En 18 hora(s) y 24 minuto(s): El equipo del Repositorio Institucional UNAL, estará fuera de la oficina del 30 de marzo al 3 de abril. Durante estos días, puedes seguir depositando tus trabajos de grado en la plataforma con normalidad. Retomaremos la publicación de los documentos en estricto orden de llegada tan pronto regresemos de nuestro receso. ¡Gracias por su comprensión!

Evaluación de expresión génica en hipocampo canino (Canis familiaris) con Síndrome de disfunción cognitiva

Vista sencilla de ítem
dc.contributor.advisorArboleda Granados, Humberto
dc.contributor.advisorPinzón Velasco, Andrés
dc.contributor.authorLópez Rodríguez, Sonia Milena
dc.contributor.researchgroupGrupo de Neurociencias-Universidad Nacional de Colombia
dc.date.accessioned2026-02-10T15:13:31Z
dc.date.available2026-02-10T15:13:31Z
dc.date.issued2025
dc.descriptionIlustraciones
dc.description.abstractLos caninos domésticos pueden desarrollar Síndrome de disfunción cognitiva canina (SDC), una patología neurodegenerativa asociada a la edad que comparte características clínico-patológicas con la enfermedad de Alzheimer, por ejemplo, el deterioro de las funciones cognitivas, la muerte neuronal progresiva en cortezas prefrontal, entorrinal e hipocampo y la formación de depósitos beta amiloide. Contrario a lo que ocurre en los humanos, la participación de un componente genético dentro de la patología en los perros ha sido escasamente evaluada. En un abordaje exploratorio descriptivo, esta investigación se propuso evaluar la expresión génica en hipocampo de pacientes con Síndrome de Disfunción Cognitiva y compararla con perros geriátricos que no presentaran la enfermedad. El diagnóstico se llevó a cabo mediante seguimiento clínico y aplicación de escalas de evaluación para SDC a caninos geriátricos en diferentes clínicas veterinarias de Bogotá. Estos sujetos, clasificados como pacientes o como controles, fueron evaluados periódicamente hasta su eutanasia. Se obtuvo muestras de hipocampo total de dos pacientes y dos controles para extracción de ARN y secuenciación. En el Análisis de Componentes Principales, se encontró que los genes TTR, APOE y GFAP mostraron perfiles de expresión diferentes al promedio tanto en pacientes como en controles. A diferencia del grupo control, el grupo de pacientes presentó abundancia de genes relacionados con desarrollo y respuesta inmune en el análisis de enriquecimiento funcional. En el análisis de vías metabólicas, el grupo de pacientes reveló una pequeña participación de genes propios de la vía metabólica de la IL-17. Estos resultados sientan las bases para evaluaciones posteriores que busquen determinar la participación de genes dentro de la fisiopatología del SDC, en especial aquellos relacionados con el desarrollo y la respuesta inmune.spa
dc.description.abstractDomestic canines naturally develop Canine Cognitive Dysfunction Syndrome (CDS), an age-related neurodegenerative disorder that shares clinicopathological features with Alzheimer's disease such as cognitive impairment, progressive neuronal loss in the prefrontal and entorhinal cortex as well as hippocampus, and the formation of beta-amyloid deposits. Opposite to humans, the role of a genetic component in canine pathology has been scarcely evaluated. In a descriptive exploratory approach, this research aimed to evaluate gene expression in the hippocampus of patients with CDS and compare it to geriatric dogs without the disease. Diagnosis was conducted through clinical follow-up and the use of rating scales for CDS in geriatric canines at various veterinary clinics in Bogotá. These subjects, classified as patients or controls, were periodically evaluated until their euthanasia. Hippocampi from two patients and two controls were obtained post-mortem for RNA extraction and sequencing. In the Principal Components Analysis, TTR, APOE, and GFAP genes exhibited different expression levels compared to other genes in patients as well as in controls. Unlike the controls, functional GO enrichment analysis revealed an abundance of genes with GO terms related to morphogenesis and development followed by immune response as the main feature in the patient's group. In this group, Kegg metabolic pathways analysis revealed genes related to the IL-17 metabolic pathway. These results might be the basis for further evaluations aimed at determining the role of genes in the pathophysiology of CCDS, especially those related to development and immune responseeng
dc.description.degreelevelMaestría
dc.description.degreenameMagister en Neurociencias
dc.description.methodsEl desarrollo metodológico del presente estudio se dividió en tres etapas: I. Evaluación clínica, clasificación y monitoreo de pacientes caninos geriátricos. II. Obtención del transcriptoma mediante RNA-seq. III. Análisis bioinformático.spa
dc.description.researchareaComportamiento animal
dc.format.extentxvii, 150 páginas
dc.format.mimetypeapplication/pdf
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/89449
dc.language.isospa
dc.publisherUniversidad Nacional de Colombia
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
dc.publisher.facultyFacultad de Medicina
dc.publisher.placeBogotá, Colombia
dc.publisher.programBogotá - Medicina - Maestría en Neurociencias
dc.relation.referencesAbbasowa, L., & Heegaard, N. H. (2014). A systematic review of amyloid-β peptides as putative mediators of the association between affective disorders and Alzheimer׳s disease. Journal of affective disorders, 168, 167–183. https://doi.org/10.1016/j.jad.2014.06.050
dc.relation.referencesAhuja, M., Buabeid, M., Abdel-Rahman, E., Majrashi, M., Parameshwaran, K., Amin, R., Ramesh, S., Thiruchelvan, K., Pondugula, S., Suppiramaniam, V., & Dhanasekaran, M. (2017). Immunological alteration & toxic molecular inductions leading to cognitive impairment & neurotoxicity in transgenic mouse model of Alzheimer's disease. Life sciences, 177, 49–59. https://doi.org/10.1016/j.lfs.2017.03.004
dc.relation.referencesAltuna, M., Urdánoz-Casado, A., Sánchez-Ruiz de Gordoa, J., Zelaya, M. V., Labarga, A., Lepesant, J. M. J., Roldán, M., Blanco-Luquin, I., Perdones, Á., Larumbe, R., Jericó, I., Echavarri, C., Méndez-López, I., Di Stefano, L., & Mendioroz, M. (2019). DNA methylation signature of human hippocampus in Alzheimer's disease is linked to neurogenesis. Clinical epigenetics, 11(1), 91. https://doi.org/10.1186/s13148-019-0672-7
dc.relation.referencesAndronie-Cioara, F. L., Ardelean, A. I., Nistor-Cseppento, C. D., Jurcau, A., Jurcau, M. C., Pascalau, N., & Marcu, F. (2023). Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer's Disease Progression. International journal of molecular sciences, 24(3), 1869. https://doi.org/10.3390/ijms24031869
dc.relation.referencesAnsari Mood, M., Rafie, S. M., Masouleh, M. N., & Aldavood, S. J. (2018). Prevalence and risk factors of cognitive dysfunction syndrome in geriatric dogs in Tehran. Journal of Veterinary Behavior, 26, 61–63
dc.relation.referencesArboleda, G. H., Yunis, J. J., Pardo, R., Gómez, C. M., Hedmont, D., Arango, G., & Arboleda, H. (2001). Apolipoprotein E genotyping in a sample of Colombian patients with Alzheimer's disease. Neuroscience letters, 305(2), 135–138. https://doi.org/10.1016/s0304-3940(01)01829-8
dc.relation.referencesAtagi, Y., Liu, C. C., Painter, M. M., Chen, X. F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., Younkin, S., Das, P., Fryer, J. D., & Bu, G. (2015). Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2). The Journal of biological chemistry, 290(43), 26043–26050. https://doi.org/10.1074/jbc.M115.679043
dc.relation.referencesAzkona, G., García-Belenguer, S., Chacón, G., Rosado, B., León, M., & Palacio, J. (2009). Prevalence and risk factors of behavioural changes associated with age-related cognitive impairment in geriatric dogs. The Journal of small animal practice, 50(2), 87–91. https://doi.org/10.1111/j.1748-5827.2008.00718.x
dc.relation.referencesBabcock, K. R., Page, J. S., Fallon, J. R., & Webb, A. E. (2021). Adult Hippocampal Neurogenesis in Aging and Alzheimer's Disease. Stem cell reports, 16(4), 681–693. https://doi.org/10.1016/j.stemcr.2021.01.019
dc.relation.referencesBang, Y., Lim, J., & Choi, H. J. (2021). Recent advances in the pathology of prodromal non-motor symptoms olfactory deficit and depression in Parkinson's disease: clues to early diagnosis and effective treatment. Archives of pharmacal research, 44(6), 588–604. https://doi.org/10.1007/s12272-021-01337-3
dc.relation.referencesBarage, S. H., & Sonawane, K. D. (2015). Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease. Neuropeptides, 52, 1–18. https://doi.org/10.1016/j.npep.2015.06.008
dc.relation.referencesBehairi, N., Belkhelfa, M., Mesbah-Amroun, H., Rafa, H., Belarbi, S., Tazir, M., & Touil-Boukoffa, C. (2015). All-trans-retinoic acid modulates nitric oxide and interleukin-17A production by peripheral blood mononuclear cells from patients with Alzheimer's disease. Neuroimmunomodulation, 22(6), 385–393. https://doi.org/10.1159/000435885
dc.relation.referencesBekiari, C., Grivas, I., Tsingotjidou, A., & Papadopoulos, G. C. (2020). Adult neurogenesis and gliogenesis in the dorsal and ventral canine hippocampus. The Journal of comparative neurology, 528(7), 1216–1230. https://doi.org/10.1002/cne.24818
dc.relation.referencesBennett S. (2012). Cognitive dysfunction in dogs: pathologic neurodegeneration or just growing older? Veterinary journal (London, England: 1997), 194(2), 141–142. https://doi.org/10.1016/j.tvjl.2012.05.009
dc.relation.referencesBlennow, K., Mattsson, N., Schöll, M., Hansson, O., & Zetterberg, H. (2015). Amyloid biomarkers in Alzheimer's disease. Trends in pharmacological sciences, 36(5), 297–309. https://doi.org/10.1016/j.tips.2015.03.002
dc.relation.referencesBoekhoorn, K., Joels, M., & Lucassen, P. J. (2006). Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiology of disease, 24(1), 1–14. https://doi.org/10.1016/j.nbd.2006.04.017
dc.relation.referencesBriley, D., Ghirardi, V., Woltjer, R., Renck, A., Zolochevska, O., Taglialatela, G., & Micci, M. A. (2016). Preserved neurogenesis in non-demented individuals with AD neuropathology. Scientific reports, 6, 27812. https://doi.org/10.1038/srep27812
dc.relation.referencesBryan J. N. (2024). Updates in Osteosarcoma. The Veterinary clinics of North America. Small animal practice, 54(3), 523–539. https://doi.org/10.1016/j.cvsm.2023.12.007
dc.relation.referencesBunyaluk, D., Srisanyong, W., & Amporn, C. (2022). Apolipoprotein E4 prevalence in different canine breeds. International Journal of Veterinary Science, 11(3), 367–372
dc.relation.referencesBuxbaum J. N. (2023). The Role of CSF Transthyretin in Human Alzheimer's Disease: Offense, Defense, or not so Innocent Bystander. Journal of integrative neuroscience, 22(6), 158. https://doi.org/10.31083/j.jin2206158
dc.relation.referencesBuxbaum, J. N., Ye, Z., Reixach, N., Friske, L., Levy, C., Das, P., Golde, T., Masliah, E., Roberts, A. R., & Bartfai, T. (2008). Transthyretin protects Alzheimer's mice from the behavioral and biochemical effects of Abeta toxicity. Proceedings of the National Academy of Sciences of the United States of America, 105(7), 2681–2686. https://doi.org/10.1073/pnas.0712197105
dc.relation.referencesCarrasquillo, M. M., Crook, J. E., Pedraza, O., Thomas, C. S., Pankratz, V. S., Allen, M., Nguyen, T., Malphrus, K. G., Ma, L., Bisceglio, G. D., Roberts, R. O., Lucas, J. A., Smith, G. E., Ivnik, R. J., Machulda, M. M., Graff-Radford, N. R., Petersen, R. C., Younkin, S. G., & Ertekin-Taner, N. (2015). Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease. Neurobiology of aging, 36(1), 60–67. https://doi.org/10.1016/j.neurobiolaging.2014.07.042
dc.relation.referencesCatchpole, B., Adams, J. P., Holder, A. L., Short, A. D., Ollier, W. E., & Kennedy, L. J. (2013). Genetics of canine diabetes mellitus: are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs?. Veterinary journal (London, England : 1997), 195(2), 139–147. https://doi.org/10.1016/j.tvjl.2012.11.013
dc.relation.referencesChambers, J. K., Uchida, K., & Nakayama, H. (2012). White matter myelin loss in the brains of aged dogs. Experimental gerontology, 47(3), 263–269. https://doi.org/10.1016/j.exger.2011.12.003
dc.relation.referencesChen, J., Liu, X., & Zhong, Y. (2020). Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases. Frontiers in aging neuroscience, 12, 566922. https://doi.org/10.3389/fnagi.2020.566922
dc.relation.referencesChoi, S. H., Leight, S. N., Lee, V. M., Li, T., Wong, P. C., Johnson, J. A., Saraiva, M. J., & Sisodia, S. S. (2007). Accelerated Abeta deposition in APPswe/PS1deltaE9 mice with hemizygous deletions of TTR (transthyretin). The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(26), 7006–7010. https://doi.org/10.1523/JNEUROSCI.1919-07.2007
dc.relation.referencesCiccone, L., Shi, C., di Lorenzo, D., Van Baelen, A. C., & Tonali, N. (2020). The Positive Side of the Alzheimer's Disease Amyloid Cross-Interactions: The Case of the Aβ 1-42 Peptide with Tau, TTR, CysC, and ApoA1. Molecules (Basel, Switzerland), 25(10), 2439. https://doi.org/10.3390/molecules25102439
dc.relation.referencesCipollini, V., Anrather, J., Orzi, F., & Iadecola, C. (2019). Th17 and Cognitive Impairment: Possible Mechanisms of Action. Frontiers in neuroanatomy, 13, 95. https://doi.org/10.3389/fnana.2019.00095
dc.relation.referencesColle M-A, Hauw J-J, Crespeau, F., Uchihara, T., Akiyama, H., Checler, F., Pageat, P., & Duykaerts, C. (2000). Vascular and parenchymal Abeta deposition in the aging dog: correlation with behavior. Neurobiology of aging, 21(5), 695–704. https://doi.org/10.1016/s0197-4580(00)00113-5
dc.relation.referencesCorder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science (New York, N.Y.), 261(5123), 921–923. https://doi.org/10.1126/science.8346443
dc.relation.referencesCosta, R., Ferreira-da-Silva, F., Saraiva, M. J., & Cardoso, I. (2008) (a). Transthyretin protects against A-beta peptide toxicity by proteolytic cleavage of the peptide: a mechanism sensitive to the Kunitz protease inhibitor. PloS one, 3(8), e2899. https://doi.org/10.1371/journal.pone.0002899
dc.relation.referencesCosta, R., Gonçalves, A., Saraiva, M. J., & Cardoso, I. (2008) (b). Transthyretin binding to A-Beta peptide--impact on A-Beta fibrillogenesis and toxicity. FEBS letters, 582(6), 936–942. https://doi.org/10.1016/j.febslet.2008.02.034
dc.relation.referencesCummings, B. J., Head, E., Afagh, A. J., Milgram, N. W., & Cotman, C. W. (1996). Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine. Neurobiology of learning and memory, 66(1), 11–23. https://doi.org/10.1006/nlme.1996.0039
dc.relation.referencesDe Nevi, E., Marco-Salazar, P., Fondevila, D., Blasco, E., Pérez, L., & Pumarola, M. (2013). Immunohistochemical study of doublecortin and nucleostemin in canine brain. European journal of histochemistry: EJH, 57(1), e9. https://doi.org/10.4081/ejh.2013.e9
dc.relation.referencesDewey, C. W., Rishniw, M., Johnson, P. J., Platt, S., Robinson, K., Sackman, J., & O'Donnell, M. (2021). Canine cognitive dysfunction patients have reduced total hippocampal volume compared with aging control dogs: A comparative magnetic resonance imaging study. Open veterinary journal, 10(4), 438–442. https://doi.org/10.4314/ovj.v10i4.11
dc.relation.referencesDickson, P. W., Aldred, A. R., Marley, P. D., Bannister, D., & Schreiber, G. (1986). Rat choroid plexus specializes in the synthesis and the secretion of transthyretin (prealbumin). Regulation of transthyretin synthesis in choroid plexus is independent from that in liver. The Journal of biological chemistry, 261(8), 3475–3478
dc.relation.referencesDubenko, O. E., Chyniak, O. S., & Potapov, O. O. (2021). Levels of proinflammatory cytokines IL-17 and IL-23 in patients with alzheimer's disease, mild cognitive impairment and vascular dementia. Wiadomosci lekarskie (Warsaw, Poland : 1960), 74(1), 68–71
dc.relation.referencesDutrow, E. V., Serpell, J. A., & Ostrander, E. A. (2022). Domestic dog lineages reveal genetic drivers of behavioral diversification. Cell, 185(25), 4737–4755.e18. https://doi.org/10.1016/j.cell.2022.11.003
dc.relation.referencesEkenstedt, K. J., & Oberbauer, A. M. (2013). Inherited epilepsy in dogs. Topics in companion animal medicine, 28(2), 51–58. https://doi.org/10.1053/j.tcam.2013.07.001
dc.relation.referencesFast, R., Schütt, T., Toft, N., Møller, A., & Berendt, M. (2013). An observational study with long-term follow-up of canine cognitive dysfunction: clinical characteristics, survival, and risk factors. Journal of veterinary internal medicine, 27(4), 822–829. https://doi.org/10.1111/jvim.12109
dc.relation.referencesFernández-Flores, F., García-Verdugo, J. M., Martín-Ibáñez, R., Herranz, C., Fondevila, D., Canals, J. M., Arús, C., & Pumarola, M. (2018). Characterization of the canine rostral ventricular-subventricular zone: Morphological, immunohistochemical, ultrastructural, and neurosphere assay studies. The Journal of comparative neurology, 526(4), 721–741. https://doi.org/10.1002/cne.24365
dc.relation.referencesFlowers, S. A., & Rebeck, G. W. (2020). APOE in the normal brain. Neurobiology of disease, 136, 104724. https://doi.org/10.1016/j.nbd.2019.104724
dc.relation.referencesFragua, V., Lepoudère, A., Leray, V., Baron, C., Araujo, J. A., Nguyen, P., & Milgram, N. W. (2017). Effects of dietary supplementation with a mixed blueberry and grape extract on working memory in aged beagle dogs. Journal of nutritional science, 6, e35. https://doi.org/10.1017/jns.2017.33
dc.relation.referencesFrank, D. (2002). Cognitive dysfunction in dogs. In Hill’s European Symposia on Canine Brain Ageing
dc.relation.referencesFuentealba, R. A., Liu, Q., Zhang, J., Kanekiyo, T., Hu, X., Lee, J. M., LaDu, M. J., & Bu, G. (2010). Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal Abeta42 uptake and lysosomal trafficking. PloS one, 5(7), e11884. https://doi.org/10.1371/journal.pone.0011884
dc.relation.referencesGarai, K., Verghese, P. B., Baban, B., Holtzman, D. M., & Frieden, C. (2014). The binding of apolipoprotein E to oligomers and fibrils of amyloid-β alters the kinetics of amyloid aggregation. Biochemistry, 53(40), 6323–6331. https://doi.org/10.1021/bi5008172
dc.relation.referencesGloeckner, S. F., Meyne, F., Wagner, F., Heinemann, U., Krasnianski, A., Meissner, B., & Zerr, I. (2008). Quantitative analysis of transthyretin, tau and amyloid-beta in patients with dementia. Journal of Alzheimer's disease : JAD, 14(1), 17–25. https://doi.org/10.3233/jad-2008-14102
dc.relation.referencesGomez-Nicola, D., Suzzi, S., Vargas-Caballero, M., Fransen, N. L., Al-Malki, H., Cebrian-Silla, A., Garcia-Verdugo, J. M., Riecken, K., Fehse, B., & Perry, V. H. (2014). Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration. Brain: a journal of neurology, 137(Pt 8), 2312–2328. https://doi.org/10.1093/brain/awu155
dc.relation.referencesGoss, J. R., Finch, C. E., & Morgan, D. G. (1991). Age-related changes in glial fibrillary acidic protein mRNA in the mouse brain. Neurobiology of aging, 12(2), 165–170. https://doi.org/10.1016/0197-4580(91)90056-p
dc.relation.referencesHan, S. H., Jung, E. S., Sohn, J. H., Hong, H. J., Hong, H. S., Kim, J. W., Na, D. L., Kim, M., Kim, H., Ha, H. J., Kim, Y. H., Huh, N., Jung, M. W., & Mook-Jung, I. (2011). Human serum transthyretin levels correlate inversely with Alzheimer's disease. Journal of Alzheimer's disease : JAD, 25(1), 77–84. https://doi.org/10.3233/JAD-2011-102145
dc.relation.referencesHart B. L. (2001). Effect of gonadectomy on subsequent development of age-related cognitive impairment in dogs. Journal of the American Veterinary Medical Association, 219(1), 51–56. https://doi.org/10.2460/javma.2001.219.51
dc.relation.referencesHatters, D. M., Peters-Libeu, C. A., & Weisgraber, K. H. (2006). Apolipoprotein E structure: insights into function. Trends in biochemical sciences, 31(8), 445–454. https://doi.org/10.1016/j.tibs.2006.06.008
dc.relation.referencesHauser, P. S., Narayanaswami, V., & Ryan, R. O. (2011). Apolipoprotein E: from lipid transport to neurobiology. Progress in lipid research, 50(1), 62–74. https://doi.org/10.1016/j.plipres.2010.09.001
dc.relation.referencesHead E. (2013). A canine model of human aging and Alzheimer's disease. Biochimica et biophysica acta, 1832(9), 1384–1389. https://doi.org/10.1016/j.bbadis.2013.03.016
dc.relation.referencesHead, E., McCleary, R., Hahn, F. F., Milgram, N. W., & Cotman, C. W. (2000) (a). Region-specific age at onset of beta-amyloid in dogs. Neurobiology of aging, 21(1), 89–96. https://doi.org/10.1016/s0197-4580(00)00093-2
dc.relation.referencesHead, E., Thornton, P. L., Tong, L., & Cotman, C. W. (2000) (b). Initiation and propagation of molecular cascades in human brain aging: insight from the canine model to promote successful aging. Progress in neuro-psychopharmacology & biological psychiatry, 24(5), 777–786. https://doi.org/10.1016/s0278-5846(00)00105-6
dc.relation.referencesHines, A. D., McGrath, S., Latham, A. S., Kusick, B., Mulligan, L., Richards, M. L., & Moreno, J. A. (2023). Activated gliosis, accumulation of amyloid β, and hyperphosphorylation of tau in aging canines with and without cognitive decline. Frontiers in aging neuroscience, 15, 1128521. https://doi.org/10.3389/fnagi.2023.1128521
dc.relation.referencesHudry, E., Klickstein, J., Cannavo, C., Jackson, R., Muzikansky, A., Gandhi, S., Urick, D., Sargent, T., Wrobleski, L., Roe, A. D., Hou, S. S., Kuchibhotla, K. V., Betensky, R. A., Spires-Jones, T., & Hyman, B. T. (2019). Opposing Roles of apolipoprotein E in aging and neurodegeneration. Life science alliance, 2(1), e201900325. https://doi.org/10.26508/lsa.201900325
dc.relation.referencesHuo, L., Du, X., Li, X., Liu, S., & Xu, Y. (2021). The Emerging Role of Neural Cell-Derived Exosomes in Intercellular Communication in Health and Neurodegenerative Diseases. Frontiers in neuroscience, 15, 738442. https://doi.org/10.3389/fnins.2021.738442
dc.relation.referencesHuppert, J., Closhen, D., Croxford, A., White, R., Kulig, P., Pietrowski, E., Bechmann, I., Becher, B., Luhmann, H. J., Waisman, A., & Kuhlmann, C. R. (2010). Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 24(4), 1023–1034. https://doi.org/10.1096/fj.09-141978
dc.relation.referencesJiang, Q., Lee, C. Y., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, N., Mann, K., Lamb, B., Willson, T. M., Collins, J. L., Richardson, J. C., Smith, J. D., Comery, T. A., Riddell, D., Holtzman, D. M., Tontonoz, P., & Landreth, G. E. (2008). ApoE promotes the proteolytic degradation of Abeta. Neuron, 58(5), 681–693. https://doi.org/10.1016/j.neuron.2008.04.010
dc.relation.referencesKanekiyo, T., Cirrito, J. R., Liu, C. C., Shinohara, M., Li, J., Schuler, D. R., Shinohara, M., Holtzman, D. M., & Bu, G. (2013). Neuronal clearance of amyloid-β by endocytic receptor LRP1. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33(49), 19276–19283. https://doi.org/10.1523/JNEUROSCI.3487-13.2013
dc.relation.referencesKarch, C. M., & Goate, A. M. (2015). Alzheimer's disease risk genes and mechanisms of disease pathogenesis. Biological psychiatry, 77(1), 43–51. https://doi.org/10.1016/j.biopsych.2014.05.006
dc.relation.referencesKebir, H., Kreymborg, K., Ifergan, I., Dodelet-Devillers, A., Cayrol, R., Bernard, M., Giuliani, F., Arbour, N., Becher, B., & Prat, A. (2007). Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nature medicine, 13(10), 1173–1175. https://doi.org/10.1038/nm1651
dc.relation.referencesKim, T. A., Syty, M. D., Wu, K., & Ge, S. (2022). Adult hippocampal neurogenesis and its impairment in Alzheimer's disease. Zoological research, 43(3), 481–496. https://doi.org/10.24272/j.issn.2095-8137.2021.479
dc.relation.referencesKimotsuki, T., Nagaoka, T., Yasuda, M., Tamahara, S., Matsuki, N., & Ono, K. (2005). Changes of magnetic resonance imaging on the brain in beagle dogs with aging. The Journal of veterinary medical science, 67(10), 961–967. https://doi.org/10.1292/jvms.67.961
dc.relation.referencesKleinert, M., Clemmensen, C., Hofmann, S. M., Moore, M. C., Renner, S., Woods, S. C., Huypens, P., Beckers, J., de Angelis, M. H., Schürmann, A., Bakhti, M., Klingenspor, M., Heiman, M., Cherrington, A. D., Ristow, M., Lickert, H., Wolf, E., Havel, P. J., Müller, T. D., & Tschöp, M. H. (2018). Animal models of obesity and diabetes mellitus. Nature reviews. Endocrinology, 14(3), 140–162. https://doi.org/10.1038/nrendo.2017.161
dc.relation.referencesKurabayashi, N., Nguyen, M. D., & Sanada, K. (2013). The G protein-coupled receptor GPRC5B contributes to neurogenesis in the developing mouse neocortex. Development (Cambridge, England), 140(21), 4335–4346. https://doi.org/10.1242/dev.099754
dc.relation.referencesLandsberg, G. M., Hunthausen, W. L., & Ackerman, L. (2013). Behavior problems of the dog and cat (3rd ed.). W. B. Saunders
dc.relation.referencesLandsberg, G. M., Nichol, J., & Araujo, J. A. (2012). Cognitive dysfunction syndrome: a disease of canine and feline brain aging. The Veterinary clinics of North America. Small animal practice, 42(4), 749–vii. https://doi.org/10.1016/j.cvsm.2012.04.003
dc.relation.referencesLee, G. S., Jeong, Y. W., Kim, J. J., Park, S. W., Ko, K. H., Kang, M., Kim, Y. K., Jung, E. M., Moon, C., Hyun, S. H., Hwang, K. C., Kim, N. H., Shin, T., Jeung, E. B., & Hwang, W. S. (2014). A canine model of Alzheimer's disease generated by overexpressing a mutated human amyloid precursor protein. International journal of molecular medicine, 33(4), 1003–1012. https://doi.org/10.3892/ijmm.2014.1636
dc.relation.referencesLi, X., & Buxbaum, J. N. (2011). Transthyretin and the brain re-visited: is neuronal synthesis of transthyretin protective in Alzheimer's disease? Molecular neurodegeneration, 6, 79. https://doi.org/10.1186/1750-1326-6-79
dc.relation.referencesLi, X., Masliah, E., Reixach, N., & Buxbaum, J. N. (2011). Neuronal production of transthyretin in human and murine Alzheimer's disease: is it protective? The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(35), 12483–12490. https://doi.org/10.1523/JNEUROSCI.2417-11.2011
dc.relation.referencesLindblad-Toh, K., Wade, C. M., Mikkelsen, T. S., Karlsson, E. K., Jaffe, D. B., Kamal, M., Clamp, M., Chang, J. L., Kulbokas, E. J., 3rd, Zody, M. C., Mauceli, E., Xie, X., Breen, M., Wayne, R. K., Ostrander, E. A., Ponting, C. P., Galibert, F., Smith, D. R., DeJong, P. J., Kirkness, E., … Lander, E. S. (2005). Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature, 438(7069), 803–819. https://doi.org/10.1038/nature04338
dc.relation.referencesLiu, C. C., Murray, M. E., Li, X., Zhao, N., Wang, N., Heckman, M. G., Shue, F., Martens, Y., Li, Y., Raulin, A. C., Rosenberg, C. L., Doss, S. V., Zhao, J., Wren, M. C., Jia, L., Ren, Y., Ikezu, T. C., Lu, W., Fu, Y., Caulfield, T., … Bu, G. (2021). APOE3-Jacksonville (V236E) variant reduces self-aggregation and risk of dementia. Science translational medicine, 13(613), eabc9375. https://doi.org/10.1126/scitranslmed.abc9375
dc.relation.referencesLiu, H., Zhang, H., & Ma, Y. (2021). Molecular mechanisms of altered adult hippocampal neurogenesis in Alzheimer's disease. Mechanisms of ageing and development, 195, 111452. https://doi.org/10.1016/j.mad.2021.111452
dc.relation.referencesLiu, Z., Qiu, A. W., Huang, Y., Yang, Y., Chen, J. N., Gu, T. T., Cao, B. B., Qiu, Y. H., & Peng, Y. P. (2019). IL-17A exacerbates neuroinflammation and neurodegeneration by activating microglia in rodent models of Parkinson's disease. Brain, behavior, and immunity, 81, 630–645. https://doi.org/10.1016/j.bbi.2019.07.026
dc.relation.referencesLój, M., Garncarz, M., & Jank, M. (2012). Genomic and genetic aspects of heart failure in dogs - a review. Acta veterinaria Hungarica, 60(1), 17–26. https://doi.org/10.1556/AVet.2012.002
dc.relation.referencesLowe, A., Dalton, M., Sidhu, K., Sachdev, P., Reynolds, B., & Valenzuela, M. (2015). Neurogenesis and precursor cell differences in the dorsal and ventral adult canine hippocampus. Neuroscience letters, 593, 107–113. https://doi.org/10.1016/j.neulet.2015.03.017
dc.relation.referencesMadari, A., Farbakova, J., Katina, S., Smolek, T., Novak, P., Weissova, T., Novak, M., & Zilka, N. (2015). Assessment of severity and progression of canine cognitive dysfunction syndrome using the CAnine DEmentia Scale (CADES). Applied Animal Behaviour Science, 171, 138–145. https://doi.org/10.1016/j.applanim.2015.08.034
dc.relation.referencesMcManus, R. M., Higgins, S. C., Mills, K. H., & Lynch, M. A. (2014). Respiratory infection promotes T cell infiltration and amyloid-β deposition in APP/PS1 mice. Neurobiology of aging, 35(1), 109–121. https://doi.org/10.1016/j.neurobiolaging.2013.07.025
dc.relation.referencesMesquita, L. L. R., Mesquita, L. P., Wadt, D., Bruhn, F. R. P., & Maiorka, P. C. (2021). Heterogenous deposition of β-amyloid in the brain of aged dogs. Neurobiology of aging, 99, 44–52. https://doi.org/10.1016/j.neurobiolaging.2020.12.006
dc.relation.referencesMoreno-Jiménez, E. P., Terreros-Roncal, J., Flor-García, M., Rábano, A., & Llorens-Martín, M. (2021). Evidences for Adult Hippocampal Neurogenesis in Humans. The Journal of neuroscience: the official journal of the Society for Neuroscience, 41(12), 2541–2553. https://doi.org/10.1523/JNEUROSCI.0675-20.2020
dc.relation.referencesMurakami, T., Ohsawa, Y., & Sunada, Y. (2008). The transthyretin gene is expressed in human and rodent dorsal root ganglia. Neuroscience letters, 436(3), 335–339. https://doi.org/10.1016/j.neulet.2008.03.063
dc.relation.referencesMuresan, V., & Ladescu Muresan, Z. (2015). Amyloid-β precursor protein: Multiple fragments, numerous transport routes and mechanisms. Experimental cell research, 334(1), 45–53. https://doi.org/10.1016/j.yexcr.2014.12.014
dc.relation.referencesNaj, A. C., Jun, G., Beecham, G. W., Wang, L. S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., Larson, E. B., Bird, T. D., Boeve, B. F., Graff-Radford, N. R., De Jager, P. L., Evans, D., Schneider, J. A., Carrasquillo, M. M., Ertekin-Taner, N., Younkin, S. G., … Schellenberg, G. D. (2011). Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nature genetics, 43(5), 436–441. https://doi.org/10.1038/ng.801
dc.relation.referencesNeilson, J. C., Hart, B. L., Cliff, K. D., & Ruehl, W. W. (2001). Prevalence of behavioral changes associated with age-related cognitive impairment in dogs. Journal of the American Veterinary Medical Association, 218(11), 1787–1791. https://doi.org/10.2460/javma.2001.218.1787
dc.relation.referencesNeus Bosch, M., Pugliese, M., Andrade, C., Gimeno-Bayón, J., Mahy, N., & Rodriguez, M. J. (2015). Amyloid-β immunotherapy reduces amyloid plaques and astroglial reaction in aged domestic dogs. Neuro-degenerative diseases, 15(1), 24–37. https://doi.org/10.1159/000368672
dc.relation.referencesNichols, N. R., Day, J. R., Laping, N. J., Johnson, S. A., & Finch, C. E. (1993). GFAP mRNA increases with age in rat and human brain. Neurobiology of aging, 14(5), 421–429. https://doi.org/10.1016/0197-4580(93)90100-p
dc.relation.referencesOberstein, T. J., Taha, L., Spitzer, P., Hellstern, J., Herrmann, M., Kornhuber, J., & Maler, J. M. (2018). Imbalance of Circulating Th17 and Regulatory T Cells in Alzheimer's Disease: A Case Control Study. Frontiers in immunology, 9, 1213. https://doi.org/10.3389/fimmu.2018.01213
dc.relation.referencesOrechio, D., Andrade Aguiar, B., Baroni Diniz, G., Cioni Bittencourt, J., Haemmerle, C. A. S., Watanabe, I. S., Miglino, M. A., & Castelucci, P. (2018). Morphological and Cellular Characterization of the Fetal Canine (Canis lupus familiaris) Subventricular Zone, Rostral Migratory Stream, and Olfactory Bulb. Anatomical record (Hoboken, N.J. : 2007), 301(9), 1570–1584. https://doi.org/10.1002/ar.23855
dc.relation.referencesOsella, M. C., Re, G., Odore, R., Girardi, C., Badino, P., Barbero, R., & Bergamasco, L. (2007). Canine cognitive dysfunction syndrome: Prevalence, clinical signs, and treatment with a neuroprotective nutraceutical. Applied Animal Behaviour Science, 105(4), 297–310
dc.relation.referencesOstrander, E. A., Wayne, R. K., Freedman, A. H., & Davis, B. W. (2017). Demographic history, selection and functional diversity of the canine genome. Nature reviews. Genetics, 18(12), 705–720. https://doi.org/10.1038/nrg.2017.67
dc.relation.referencesOstrander, E. A., Dreger, D. L., & Evans, J. M. (2019). Canine Cancer Genomics: Lessons for Canine and Human Health. Annual review of animal biosciences, 7, 449–472. https://doi.org/10.1146/annurev-animal-030117-014523
dc.relation.referencesO'Sullivan, S. S., Johnson, M., Williams, D. R., Revesz, T., Holton, J. L., Lees, A. J., & Perry, E. K. (2011). The effect of drug treatment on neurogenesis in Parkinson's disease. Movement disorders: official journal of the Movement Disorder Society, 26(1), 45–50. https://doi.org/10.1002/mds.23340
dc.relation.referencesOzawa, M., Chambers, J. K., Uchida, K., & Nakayama, H. (2016). The Relation between canine cognitive dysfunction and age-related brain lesions. The Journal of veterinary medical science, 78(6), 997–1006. https://doi.org/10.1292/jvms.15-0624
dc.relation.referencesPacker, R. M. A., McGreevy, P. D., Salvin, H. E., Valenzuela, M. J., Chaplin, C. M., & Volk, H. A. (2018). Cognitive dysfunction in naturally occurring canine idiopathic epilepsy. PloS one, 13(2), e0192182. https://doi.org/10.1371/journal.pone.0192182
dc.relation.referencesPakozdy, A., Patzl, M., Zimmermann, L., Jokinen, T. S., Glantschnigg, U., Kelemen, A., & Hasegawa, D. (2015). LGI Proteins and Epilepsy in Human and Animals. Journal of veterinary internal medicine, 29(4), 997–1005. https://doi.org/10.1111/jvim.12610
dc.relation.referencesPalmer, J. M., Huentelman, M., & Ryan, L. (2023). More than just risk for Alzheimer's disease: APOE ε4's impact on the aging brain. Trends in neurosciences, 46(9), 750–763. https://doi.org/10.1016/j.tins.2023.06
dc.relation.referencesPapaioannou, N., Tooten, P. C., van Ederen, A. M., Bohl, J. R., Rofina, J., Tsangaris, T., & Gruys, E. (2001). Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 8(1), 11–21. https://doi.org/10.3109/13506120108993810
dc.relation.referencesPartridge, B., & Rossmeisl, J. H., Jr (2020). Companion animal models of neurological disease. Journal of neuroscience methods, 331, 108484. https://doi.org/10.1016/j.jneumeth.2019.108484
dc.relation.referencesPekcec, A., Baumgärtner, W., Bankstahl, J. P., Stein, V. M., & Potschka, H. (2008). Effect of aging on neurogenesis in the canine brain. Aging cell, 7(3), 368–374. https://doi.org/10.1111/j.1474-9726.2008.00392.x
dc.relation.referencesPerry, E. K., Johnson, M., Ekonomou, A., Perry, R. H., Ballard, C., & Attems, J. (2012). Neurogenic abnormalities in Alzheimer's disease differ between stages of neurogenesis and are partly related to cholinergic pathology. Neurobiology of disease, 47(2), 155–162. https://doi.org/10.1016/j.nbd.2012.03.033
dc.relation.referencesPhochantachinda, S., Chantong, B., Reamtong, O., & Chatchaisak, D. (2023). Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy. Frontiers in veterinary science, 10, 1258244. https://doi.org/10.3389/fvets.2023.1258244
dc.relation.referencesPrins, S., de Kam, M. L., Teunissen, C. E., & Groeneveld, G. J. (2022). Inflammatory plasma biomarkers in subjects with preclinical Alzheimer's disease. Alzheimer's research & therapy, 14(1), 106. https://doi.org/10.1186/s13195-022-01051-2
dc.relation.referencesRahman, M. T., Ghosh, C., Hossain, M., Linfield, D., Rezaee, F., Janigro, D., Marchi, N., & van Boxel-Dezaire, A. H. H. (2018). IFN-γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases. Biochemical and biophysical research communications, 507(1-4), 274–279. https://doi.org/10.1016/j.bbrc.2018.11.021
dc.relation.referencesRajapaksha E. (2018). Special Considerations for Diagnosing Behavior Problems in Older Pets. The Veterinary clinics of North America. Small animal practice, 48(3), 443–456. https://doi.org/10.1016/j.cvsm.2017.12.010
dc.relation.referencesRamos-Campoy, O., Comas-Albertí, A., Hervás, D., Borrego-Écija, S., Bosch, B., Sandoval, J., Fort-Aznar, L., Moreno-Izco, F., Fernández-Villullas, G., Molina-Porcel, L., Balasa, M., Lladó, A., Sánchez-Valle, R., & Antonell, A. (2024). Genome-Wide DNA Methylation in Early-Onset-Dementia Patients Brain Tissue and Lymphoblastoid Cell Lines. International journal of molecular sciences, 25(10), 5445. https://doi.org/10.3390/ijms25105445
dc.relation.referencesRaulin, A. C., Martens, Y. A., & Bu, G. (2022). Lipoproteins in the Central Nervous System: From Biology to Pathobiology. Annual review of biochemistry, 91, 731–759. https://doi.org/10.1146/annurev-biochem-032620-104801
dc.relation.referencesReitz C. (2015). Genetic diagnosis and prognosis of Alzheimer's disease: challenges and opportunities. Expert review of molecular diagnostics, 15(3), 339–348. https://doi.org/10.1586/14737159.2015.1002469
dc.relation.referencesRibeiro, C. A., Saraiva, M. J., & Cardoso, I. (2012). Stability of the transthyretin molecule as a key factor in the interaction with a-beta peptide--relevance in Alzheimer's disease. PloS one, 7(9), e45368. https://doi.org/10.1371/journal.pone.0045368
dc.relation.referencesRosenthal, S. L., & Kamboh, M. I. (2014). Late-Onset Alzheimer's Disease Genes and the Potentially Implicated Pathways. Current genetic medicine reports, 2(2), 85–101. https://doi.org/10.1007/s40142-014-0034-x
dc.relation.referencesRoy, M., Kim, N., Kim, K., Chung, W. H., Achawanantakun, R., Sun, Y., & Wayne, R. (2013). Analysis of the canine brain transcriptome with an emphasis on the hypothalamus and cerebral cortex. Mammalian genome : official journal of the International Mammalian Genome Society, 24(11-12), 484–499. https://doi.org/10.1007/s00335-013-9480-0
dc.relation.referencesRusbridge, C., Salguero, F. J., David, M. A., Faller, K. M. E., Bras, J. T., Guerreiro, R. J., Richard-Londt, A. C., Grainger, D., Head, E., Brandner, S. G. P., Summers, B., Hardy, J., & Tayebi, M. (2018). An Aged Canid with Behavioral Deficits Exhibits Blood and Cerebrospinal Fluid Amyloid Beta Oligomers. Frontiers in aging neuroscience, 10, 7. https://doi.org/10.3389/fnagi.2018.00007
dc.relation.referencesRussell, M. J., Bobik, M., White, R. G., Hou, Y., Benjamin, S. A., & Geddes, J. W. (1996). Age-specific onset of beta-amyloid in beagle brains. Neurobiology of aging, 17(2), 269–273. https://doi.org/10.1016/0197-4580(95)02072-1
dc.relation.referencesSalvin, H. E., McGreevy, P. D., Sachdev, P. S., & Valenzuela, M. J. (2011). The canine cognitive dysfunction rating scale (CCDR): a data-driven and ecologically relevant assessment tool. Veterinary journal (London, England: 1997), 188(3), 331–336. https://doi.org/10.1016/j.tvjl.2010.05.014
dc.relation.referencesSalvin, H. E., McGreevy, P. D., Sachdev, P. S., & Valenzuela, M. J. (2010). Under diagnosis of canine cognitive dysfunction: a cross-sectional survey of older companion dogs. Veterinary journal (London, England: 1997), 184(3), 277–281. https://doi.org/10.1016/j.tvjl.2009.11.007
dc.relation.referencesSándor, S., & Kubinyi, E. (2019). Genetic Pathways of Aging and Their Relevance in the Dog as a Natural Model of Human Aging. Frontiers in genetics, 10, 948. https://doi.org/10.3389/fgene.2019.00948
dc.relation.referencesSaponaro, F., Kim, J. H., & Chiellini, G. (2020). Transthyretin Stabilization: An Emerging Strategy for the Treatment of Alzheimer's Disease?. International journal of molecular sciences, 21(22), 8672. https://doi.org/10.3390/ijms21228672
dc.relation.referencesSarasa, L., Allué, J. A., Pesini, P., González-Martínez, A., & Sarasa, M. (2013). Identification of β-amyloid species in canine cerebrospinal fluid by mass spectrometry. Neurobiology of aging, 34(9), 2125–2132. https://doi.org/10.1016/j.neurobiolaging.2013.03.009
dc.relation.referencesSarasa, L., Gallego, C., Monleón, I., Olvera, A., Canudas, J., Montañés, M., Pesini, P., & Sarasa, M. (2010). Cloning, sequencing and expression in the dog of the main amyloid precursor protein isoforms and some of the enzymes related with their processing. Neuroscience, 171(4), 1091–1101. https://doi.org/10.1016/j.neuroscience.2010.09.042
dc.relation.referencesSaresella, M., Calabrese, E., Marventano, I., Piancone, F., Gatti, A., Alberoni, M., Nemni, R., & Clerici, M. (2011). Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer's disease. Brain, behavior, and immunity, 25(3), 539–547. https://doi.org/10.1016/j.bbi.2010.12.004
dc.relation.referencesSchmidt, F., Boltze, J., Jäger, C., Hofmann, S., Willems, N., Seeger, J., Härtig, W., & Stolzing, A. (2015). Detection and Quantification of β-Amyloid, Pyroglutamyl Aβ, and Tau in Aged Canines. Journal of neuropathology and experimental neurology, 74(9), 912–923. https://doi.org/10.1097/NEN.0000000000000230
dc.relation.referencesSchütt, T., Helboe, L., Pedersen, L. Ø., Waldemar, G., Berendt, M., & Pedersen, J. T. (2016). Dogs with Cognitive Dysfunction as a Spontaneous Model for Early Alzheimer's Disease: A Translational Study of Neuropathological and Inflammatory Markers. Journal of Alzheimer's disease : JAD, 52(2), 433–449. https://doi.org/10.3233/JAD-151085
dc.relation.referencesSetó-Salvia, N. (2010). Genética en la enfermedad de Alzheimer. Revista Neurológica, 50(6), 360–364
dc.relation.referencesShaffer L. G. (2019). Special issue on canine genetics: animal models for human disease and gene therapies, new discoveries for canine inherited diseases, and standards and guidelines for clinical genetic testing for domestic dogs. Human genetics, 138(5), 437–440. https://doi.org/10.1007/s00439-019-02025-5
dc.relation.referencesShi, H., Belbin, O., Medway, C., Brown, K., Kalsheker, N., Carrasquillo, M., Proitsi, P., Powell, J., Lovestone, S., Goate, A., Younkin, S., Passmore, P., Genetic and Environmental Risk for Alzheimer's Disease Consortium, Morgan, K., & Alzheimer's Research UK Consortium (2012). Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS). Neurobiology of aging, 33(8), 1849.e5–1849.18. https://doi.org/10.1016/j.neurobiolaging.2012.02.014
dc.relation.referencesShimada, A., Kuwamura, M., Awakura, T., Umemura, T., & Itakura, C. (1992). An immunohistochemical and ultrastructural study on age-related astrocytic gliosis in the central nervous system of dogs. The Journal of veterinary medical science, 54(1), 29–36. https://doi.org/10.1292/jvms.54.29
dc.relation.referencesSiffrin, V., Radbruch, H., Glumm, R., Niesner, R., Paterka, M., Herz, J., Leuenberger, T., Lehmann, S. M., Luenstedt, S., Rinnenthal, J. L., Laube, G., Luche, H., Lehnardt, S., Fehling, H. J., Griesbeck, O., & Zipp, F. (2010). In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity, 33(3), 424–436. https://doi.org/10.1016/j.immuni.2010.08.018
dc.relation.referencesSiwak-Tapp, C. T., Head, E., Muggenburg, B. A., Milgram, N. W., & Cotman, C. W. (2007). Neurogenesis decreases with age in the canine hippocampus and correlates with cognitive function. Neurobiology of learning and memory, 88(2), 249–259. https://doi.org/10.1016/j.nlm.2007.05.001
dc.relation.referencesSorrentino, P., Iuliano, A., Polverino, A., Jacini, F., & Sorrentino, G. (2014). The dark sides of amyloid in Alzheimer's disease pathogenesis. FEBS letters, 588(5), 641–652. https://doi.org/10.1016/j.febslet.2013.12.038
dc.relation.referencesSousa, J. C., Cardoso, I., Marques, F., Saraiva, M. J., & Palha, J. A. (2007). Transthyretin and Alzheimer's disease: where in the brain?. Neurobiology of aging, 28(5), 713–718. https://doi.org/10.1016/j.neurobiolaging.2006.03.015
dc.relation.referencesSousa, M. M., & Saraiva, M. J. (2008). Transthyretin is not expressed by dorsal root ganglia cells. Experimental neurology, 214(2), 362–365. https://doi.org/10.1016/j.expneurol.2008.08.019
dc.relation.referencesSparkman, N. L., & Johnson, R. W. (2008). Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation, 15(4-6), 323–330. https://doi.org/10.1159/000156474
dc.relation.referencesSt-Amour, I., Bosoi, C. R., Paré, I., Ignatius Arokia Doss, P. M., Rangachari, M., Hébert, S. S., Bazin, R., & Calon, F. (2019). Peripheral adaptive immunity of the triple transgenic mouse model of Alzheimer's disease. Journal of neuroinflammation, 16(1), 3. https://doi.org/10.1186/s12974-018-1380-5
dc.relation.referencesStein, T. D., & Johnson, J. A. (2002). Lack of neurodegeneration in transgenic mice overexpressing mutant amyloid precursor protein is associated with increased levels of transthyretin and the activation of cell survival pathways. The Journal of neuroscience : the official journal of the Society for Neuroscience, 22(17), 7380–7388. https://doi.org/10.1523/JNEUROSCI.22-17-07380.2002
dc.relation.referencesSzabó, D., Miklósi, Á., & Kubinyi, E. (2018). Owner reported sensory impairments affect behavioural signs associated with cognitive decline in dogs. Behavioural processes, 157, 354–360. https://doi.org/10.1016/j.beproc.2018.07.013
dc.relation.referencesTai, L. M., Bilousova, T., Jungbauer, L., Roeske, S. K., Youmans, K. L., Yu, C., Poon, W. W., Cornwell, L. B., Miller, C. A., Vinters, H. V., Van Eldik, L. J., Fardo, D. W., Estus, S., Bu, G., Gylys, K. H., & Ladu, M. J. (2013). Levels of soluble apolipoprotein E/amyloid-β (Aβ) complex are reduced and oligomeric Aβ increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples. The Journal of biological chemistry, 288(8), 5914–5926. https://doi.org/10.1074/jbc.M112.442103
dc.relation.referencesTalwar, P., Silla, Y., Grover, S., Gupta, M., Agarwal, R., Kushwaha, S., & Kukreti, R. (2014). Genomic convergence and network analysis approach to identify candidate genes in Alzheimer's disease. BMC genomics, 15(1), 199. https://doi.org/10.1186/1471-2164-15-199
dc.relation.referencesTanzi R. E. (2013). A brief history of Alzheimer's disease gene discovery. Journal of Alzheimer's disease: JAD, 33 Suppl 1, S5–S13. https://doi.org/10.3233/JAD-2012-129044
dc.relation.referencesThomsen, B. B., Madsen, C., Krohn, K. T., Thygesen, C., Schütt, T., Metaxas, A., Darvesh, S., Agerholm, J. S., Wirenfeldt, M., Berendt, M., & Finsen, B. (2021). Mild Microglial Responses in the Cortex and Perivascular Macrophage Infiltration in Subcortical White Matter in Dogs with Age-Related Dementia Modelling Prodromal Alzheimer's Disease. Journal of Alzheimer's disease: JAD, 82(2), 575–592. https://doi.org/10.3233/JAD-210040
dc.relation.referencesTobin, M. K., Musaraca, K., Disouky, A., Shetti, A., Bheri, A., Honer, W. G., Kim, N., Dawe, R. J., Bennett, D. A., Arfanakis, K., & Lazarov, O. (2019). Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer's Disease Patients. Cell stem cell, 24(6), 974–982.e3. https://doi.org/10.1016/j.stem.2019.05.003
dc.relation.referencesTorp, R., Head, E., & Cotman, C. W. (2000). Ultrastructural analyses of beta-amyloid in the aged dog brain: neuronal beta-amyloid is localized to the plasma membrane. Progress in neuro-psychopharmacology & biological psychiatry, 24(5), 801–810. https://doi.org/10.1016/s0278-5846(00)00107-x
dc.relation.referencesVan Acker, Z. P., Bretou, M., & Annaert, W. (2019). Endo-lysosomal dysregulations and late-onset Alzheimer's disease: impact of genetic risk factors. Molecular neurodegeneration, 14(1), 20. https://doi.org/10.1186/s13024-019-0323-7
dc.relation.referencesVelayudhan, L., Killick, R., Hye, A., Kinsey, A., Güntert, A., Lynham, S., Ward, M., Leung, R., Lourdusamy, A., To, A. W., Powell, J., & Lovestone, S. (2012). Plasma transthyretin as a candidate marker for Alzheimer's disease. Journal of Alzheimer's disease : JAD, 28(2), 369–375. https://doi.org/10.3233/JAD-2011-110611
dc.relation.referencesVerghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011). Apolipoprotein E in Alzheimer's disease and other neurological disorders. The Lancet. Neurology, 10(3), 241–252. https://doi.org/10.1016/S1474-4422(10)70325-2
dc.relation.referencesVieira, M., & Saraiva, M. J. (2014). Transthyretin: a multifaceted protein. Biomolecular concepts, 5(1), 45–54. https://doi.org/10.1515/bmc-2013-0038
dc.relation.referencesVikartovska, Z., Farbakova, J., Smolek, T., Hanes, J., Zilka, N., Hornakova, L., Humenik, F., Maloveska, M., Hudakova, N., & Cizkova, D. (2021). Novel Diagnostic Tools for Identifying Cognitive Impairment in Dogs: Behavior, Biomarkers, and Pathology. Frontiers in veterinary science, 7, 551895. https://doi.org/10.3389/fvets.2020.551895
dc.relation.referencesWalton, R. M., Parmentier, T., & Wolfe, J. H. (2013). Postnatal neural precursor cell regions in the rostral subventricular zone, hippocampal subgranular zone and cerebellum of the dog (Canis lupus familiaris). Histochemistry and cell biology, 139(3), 415–429. https://doi.org/10.1007/s00418-012-1053-x
dc.relation.referencesWang, W. Y., Tan, M. S., Yu, J. T., & Tan, L. (2015). Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease. Annals of translational medicine, 3(10), 136. https://doi.org/10.3978/j.issn.2305-5839.2015.03.49
dc.relation.referencesWati, H., Kawarabayashi, T., Matsubara, E., Kasai, A., Hirasawa, T., Kubota, T., Harigaya, Y., Shoji, M., & Maeda, S. (2009). Transthyretin accelerates vascular Abeta deposition in a mouse model of Alzheimer's disease. Brain pathology (Zurich, Switzerland), 19(1), 48–57. https://doi.org/10.1111/j.1750-3639.2008.00166.x
dc.relation.referencesWinner, B., & Winkler, J. (2015). Adult neurogenesis in neurodegenerative diseases. Cold Spring Harbor perspectives in biology, 7(4), a021287. https://doi.org/10.1101/cshperspect.a021287
dc.relation.referencesWojkowska, D. W., Szpakowski, P., & Glabinski, A. (2017). Interleukin 17A Promotes Lymphocytes Adhesion and Induces CCL2 and CXCL1 Release from Brain Endothelial Cells. International journal of molecular sciences, 18(5), 1000. https://doi.org/10.3390/ijms18051000
dc.relation.referencesWu, L., Rosa-Neto, P., Hsiung, G. Y., Sadovnick, A. D., Masellis, M., Black, S. E., Jia, J., & Gauthier, S. (2012). Early-onset familial Alzheimer's disease (EOFAD). The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 39(4), 436–445. https://doi.org/10.1017/s0317167100013949
dc.relation.referencesWu, P. (2015). Associations between apolipoprotein A gene polymorphisms and Alzheimer’s disease risk in a large Chinese Han population. Clinical Interventions in Aging, 10, 371–378
dc.relation.referencesYandell, M., & Ence, D. (2012). A beginner's guide to eukaryotic genome annotation. Nature reviews. Genetics, 13(5), 329–342. https://doi.org/10.1038/nrg3174
dc.relation.referencesYang, J., Kou, J., Lalonde, R., & Fukuchi, K. I. (2017). Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer's disease. Brain, behavior, and immunity, 65, 262–273. https://doi.org/10.1016/j.bbi.2017.05.012
dc.relation.referencesYeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016). TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron, 91(2), 328–340. https://doi.org/10.1016/j.neuron.2016.06.015
dc.relation.referencesYoussef, S. A., Capucchio, M. T., Rofina, J. E., Chambers, J. K., Uchida, K., Nakayama, H., & Head, E. (2016). Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases. Veterinary pathology, 53(2), 327–348. https://doi.org/10.1177/0300985815623997
dc.relation.referencesZenaro, E., Pietronigro, E., Della Bianca, V., Piacentino, G., Marongiu, L., Budui, S., Turano, E., Rossi, B., Angiari, S., Dusi, S., Montresor, A., Carlucci, T., Nanì, S., Tosadori, G., Calciano, L., Catalucci, D., Berton, G., Bonetti, B., & Constantin, G. (2015). Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin. Nature medicine, 21(8), 880–886. https://doi.org/10.1038/nm.3913
dc.relation.referencesZhang, F., & Jiang, L. (2015). Neuroinflammation in Alzheimer's disease. Neuropsychiatric disease and treatment, 11, 243–256. https://doi.org/10.2147/NDT.S75546
dc.relation.referencesZhang, J., Ke, K. F., Liu, Z., Qiu, Y. H., & Peng, Y. P. (2013). Th17 cell-mediated neuroinflammation is involved in neurodegeneration of aβ1-42-induced Alzheimer's disease model rats. PloS one, 8(10), e75786. https://doi.org/10.1371/journal.pone.0075786
dc.relation.referencesZhou, L., Chan, K. H., Chu, L. W., Kwan, J. S., Song, Y. Q., Chen, L. H., Ho, P. W., Cheng, O. Y., Ho, J. W., & Lam, K. S. (2012). Plasma amyloid-β oligomers level is a biomarker for Alzheimer's disease diagnosis. Biochemical and biophysical research communications, 423(4), 697–702. https://doi.org/10.1016/j.bbrc.2012.06.017
dc.relation.referencesZimmermann, J., Krauthausen, M., Hofer, M. J., Heneka, M. T., Campbell, I. L., & Müller, M. (2013). CNS-targeted production of IL-17A induces glial activation, microvascular pathology and enhances the neuroinflammatory response to systemic endotoxemia. PloS one, 8(2), e57307. https://doi.org/10.1371/journal.pone.0057307
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.licenseReconocimiento 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.armarcEnfermedades neurodegenerativasspa
dc.subject.armarcExpresión del genspa
dc.subject.bnePerros -- Envejecimientospa
dc.subject.ddc610 - Medicina y salud
dc.subject.ddc570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales
dc.subject.decsCognitive Dysfunction -- Geneticseng
dc.subject.decsDisfunción cognitiva -- Genéticaspa
dc.subject.decsPerfilación de la expresión génicaspa
dc.subject.decsGene Expression Profilingeng
dc.subject.decsEnfermedades de los perrosspa
dc.subject.decsDog Diseaseseng
dc.subject.lccNervous system -- Degenerationeng
dc.subject.lccGene expressioneng
dc.subject.proposalDisfunción cognitiva caninaspa
dc.subject.proposalNeurodegeneraciónspa
dc.subject.proposalTranscriptomaspa
dc.subject.proposalHipocampo caninospa
dc.subject.proposalNeurogénesis hipocampal adultaspa
dc.subject.proposalNeuroinflamaciónspa
dc.subject.proposalAstrocitosisspa
dc.subject.proposalCanine cognitive dysfunctioneng
dc.subject.proposalNeurodegenerationeng
dc.subject.proposalTranscriptomic analysiseng
dc.subject.proposalCanine hippocampuseng
dc.subject.proposalAdult hippocampal neurogenesiseng
dc.subject.proposalNeuroinflammationeng
dc.subject.proposalAstrocytosiseng
dc.titleEvaluación de expresión génica en hipocampo canino (Canis familiaris) con Síndrome de disfunción cognitivaspa
dc.title.translatedGenic expression evaluation in canine hippocampus (Canis familiaris) with Cognitive Dysfunction Syndromeeng
dc.typeTrabajo de grado - Maestría
dc.type.coarhttp://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.redcolhttp://purl.org/redcol/resource_type/TM
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dcterms.audience.professionaldevelopmentInvestigadores
dcterms.audience.professionaldevelopmentEstudiantes
dcterms.audience.professionaldevelopmentEspecializada
dcterms.audience.professionaldevelopmentMaestros
dcterms.audience.professionaldevelopmentPúblico general
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2

Archivos

Bloque original

Mostrando 1 - 1 de 1
Miniatura
Nombre:
52886555.2025.pdf
Tamaño:
2.53 MB
Formato:
Adobe Portable Document Format
Descripción:
Tesis de Maestría en Neurociencias
Descargar

Bloque de licencias

Mostrando 1 - 1 de 1
Miniatura
Nombre:
license.txt
Tamaño:
5.74 KB
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar

Colecciones

Maestría en Neurociencias