{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T22:59:38Z","timestamp":1788044378368,"version":"build-2784847793"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"18","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,5,2]]},"abstract":"<jats:p>Alzheimer\u2019s disease is a debilitating neurodegenerative disorder with no cure and few treatment options. In early stages of Alzheimer\u2019s disease, impaired metabolism and functional connectivity of the retrosplenial cortex strongly predict future cognitive impairments. Therefore, understanding Alzheimer\u2019s disease\u2013related deficits in the retrosplenial cortex is critical for understanding the origins of cognitive impairment and identifying early treatment targets. Using the 5xFAD mouse model, we discovered early, sex-dependent alterations in parvalbumin-interneuron transcriptomic profiles. This corresponded with impaired parvalbumin-interneuron activity, which was sufficient to induce cognitive impairments and dysregulate retrosplenial functional connectivity. In fMRI scans from patients with mild cognitive impairment and Alzheimer\u2019s disease, we observed a similar sex-dependent dysregulation of retrosplenial cortex functional connectivity and, in postmortem tissue from subjects with Alzheimer\u2019s disease, a loss of parvalbumin interneurons. Reversal of cognitive deficits by stimulation of parvalbumin interneurons in the retrosplenial cortex suggests that this may serve as a promising therapeutic strategy.<\/jats:p>","DOI":"10.1126\/sciadv.adt8976","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T22:03:58Z","timestamp":1746050638000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":17,"title":["Impaired parvalbumin interneurons in the retrosplenial cortex as the cause of sex-dependent vulnerability in Alzheimer\u2019s disease"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-0875","authenticated-orcid":true,"given":"Dylan J.","family":"Terstege","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada."},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada."},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4583-8950","authenticated-orcid":true,"given":"Bo Young","family":"Ahn","sequence":"additional","affiliation":[{"name":"Applied Spatial Omics Centre, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6218-8609","authenticated-orcid":true,"given":"Heewon","family":"Seo","sequence":"additional","affiliation":[{"name":"Applied Spatial Omics Centre, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3217-7455","authenticated-orcid":true,"given":"Kabirat","family":"Adigun","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada."},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-9972","authenticated-orcid":true,"given":"Liisa A. 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