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Douglas Alzheimer\u2019s Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate \u2018pro-aging\u2019 or \u2018pro-youthful\u2019 effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear. We examined five previously identified brain rejuvenation factors in cerebrospinal fluid of adults with autosomal dominant forms of frontotemporal dementia and sporadic Alzheimer\u2019s disease. Our frontotemporal dementia cohort included 100 observationally followed adults carrying autosomal dominant frontotemporal dementia mutations (Mage = 49.6; 50% female; 43% C9orf72, 24% GRN, 33% MAPT) and 62 non-carriers (Mage = 52.6; 45% female) with cerebrospinal fluid analysed on Somascan, and longitudinal (Mvisits = 3 years, range 1\u20137 years) neuropsychological and functional assessments and plasma neurofilament light chain. Our Alzheimer\u2019s disease cohort included 35 adults with sporadic Alzheimer\u2019s disease (Mage = 69.4; 60% female) and 56 controls (Mage = 68.8, 50% female) who completed the same cerebrospinal fluid and clinical outcome measures cross-sectionally. Levels of C-C motif chemokine ligand 11, C-C motif chemokine ligand 2, beta-2-micorglobulin, bone gamma-carboxyglutamate protein (aka Osteocalcin) and colony stimulating factor 2 in cerebrospinal fluid were linearly combined into a composite score, with higher values reflecting \u2018pro-youthful\u2019 levels. In genetic frontotemporal dementia, higher baseline cerebrospinal fluid rejuvenation proteins predicted slower decline across cognitive, functional, and neurofilament light chain trajectories; estimates were similar across genotypes. In transdiagnostic analyses, higher cerebrospinal fluid rejuvenation proteins associated with better functional, cognitive, and neurofilament light chain outcomes in adults with sporadic Alzheimer\u2019s disease. Proteins with pre-clinical evidence for brain rejuvenation show translational clinical relevance in adults with Alzheimer\u2019s disease and related dementias and warrant further investigation.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae432","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T15:26:46Z","timestamp":1736954806000},"source":"Crossref","is-referenced-by-count":5,"title":["Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0610-6933","authenticated-orcid":false,"given":"Kaitlin B","family":"Casaletto","sequence":"first","affiliation":[{"name":"Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowan","family":"Saloner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kornak","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M","family":"Staffaroni","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul","family":"Villeda","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California , San Francisco, CA 94143 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Paolillo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M","family":"VandeBunte","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire J","family":"Cadwallader","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argentina","family":"Lario Lago","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA 94158 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