{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:34:42Z","timestamp":1772714082162,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-104921RB-I00"],"award-info":[{"award-number":["PID2019-104921RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010434","name":"\u201cla Caixa\u201d Foundation","doi-asserted-by":"publisher","award":["CI20-00207"],"award-info":[{"award-number":["CI20-00207"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Understanding the mechanisms involved in cognitive resilience in Alzheimer\u2019s disease (AD) represents a promising strategy to identify novel treatments for dementia in AD. Previous findings from our group revealed that the study of aged-Tg2576 cognitive resilient individuals is a suitable tool for this purpose. In the present study, we performed a transcriptomic analysis using the prefrontal cortex of demented and resilient Tg2576 transgenic AD mice. We have been able to hypothesize that pathways involved in inflammation, amyloid degradation, memory function, and neurotransmission may be playing a role on cognitive resilience in AD. Intriguingly, the results obtained in this study are suggestive of a reduction of the influx of peripheral immune cells into the brain on cognitive resilient subjects. Indeed, CD4 mRNA expression is significantly reduced on Tg2576 mice with cognitive resilience. For further validation of this result, we analyzed CD4 expression in human AD samples, including temporal cortex and peripheral blood mononuclear cells (PBMC). Interestingly, we have found a negative correlation between CD4 mRNA levels in the periphery and the score in the Mini-Mental State Exam of AD patients. These findings highlight the importance of understanding the role of the immune system on the development of neurodegenerative diseases and points out to the infiltration of CD4+ cells in the brain as a key player of cognitive dysfunction in AD.<\/jats:p>","DOI":"10.3390\/ijms22179120","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:12:22Z","timestamp":1629843142000},"page":"9120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Identifying the Main Functional Pathways Associated with Cognitive Resilience to Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1693-3361","authenticated-orcid":false,"given":"Marta","family":"P\u00e9rez-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Disease, Neurosciences Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain"},{"name":"Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Badesso","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease, Neurosciences Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain"},{"name":"Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease, Neurosciences Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0547-681X","authenticated-orcid":false,"given":"Elizabeth","family":"Guruceaga","sequence":"additional","affiliation":[{"name":"IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain"},{"name":"Bioinformatics Platform, Centro de Investigaci\u00f3n M\u00e9dica Aplicada, Instituto de Investigaci\u00f3n Sanitaria de Navarra, ProteoRed-ISCIII, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1926-0972","authenticated-orcid":false,"given":"Alberto","family":"P\u00e9rez-Mediavilla","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease, Neurosciences Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain"},{"name":"Department of Biochemistry and Genetics, School of Sciences, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Garc\u00eda-Osta","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease, Neurosciences Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar","family":"Cuadrado-Tejedor","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease, Neurosciences Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain"},{"name":"Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tanaka, M., T\u00f6r\u00f6k, N., and V\u00e9csei, L. 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