{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:51:28Z","timestamp":1781661088212,"version":"3.54.5"},"reference-count":52,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,12,6]]},"abstract":"<jats:p>Background: Alzheimer\u2019s disease and related dementias (ADRD) involve biological processes that begin years to decades before onset of clinical symptoms. The plasma proteome can offer insight into brain aging and risk of incident dementia among cognitively healthy adults. Objective: To identify biomarkers and biological pathways associated with neuroimaging measures and incident dementia in two large community-based cohorts by applying a correlation-based network analysis to the plasma proteome. Methods: Weighted co-expression network analysis of 1,305 plasma proteins identified four modules of co-expressed proteins, which were related to MRI brain volumes and risk of incident dementia over a median 20-year follow-up in Framingham Heart Study (FHS) Offspring cohort participants (n = 1,861). Analyses were replicated in the Cardiovascular Health Study (CHS) (n = 2,117, mean 6-year follow-up). Results: Two proteomic modules, one related to protein clearance and synaptic maintenance (M2) and a second to inflammation (M4), were associated with total brain volume in FHS (M2: p = 0.014; M4: p = 4.2\u00d710\u20135). These modules were not significantly associated with hippocampal volume, white matter hyperintensities, or incident all-cause or AD dementia. Associations with TCBV did not replicate in CHS, an older cohort with a greater burden of comorbidities. Conclusions: Proteome networks implicate an early role for biological pathways involving inflammation and synaptic function in preclinical brain atrophy, with implications for clinical dementia.<\/jats:p>","DOI":"10.3233\/jad-230145","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T12:40:18Z","timestamp":1700829618000},"page":"1767-1780","source":"Crossref","is-referenced-by-count":4,"title":["Proteome Network Analysis Identifies Potential Biomarkers for Brain Aging"],"prefix":"10.1177","volume":"96","author":[{"given":"Meghan I.","family":"Short","sequence":"first","affiliation":[{"name":"Glenn Biggs Institute for Alzheimer\u2019s & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, TX, USA"},{"name":"Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA"},{"name":"Department of Medicine, Tufts University School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison E.","family":"Fohner","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, WA, USA"},{"name":"Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5vard K.","family":"Skjellegrind","sequence":"additional","affiliation":[{"name":"HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Levanger, Norway"},{"name":"Levanger Hospital, Nord-Tr\u00f8ndelag Hospital Trust, Levanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Beiser","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA"},{"name":"Framingham Heart Study, Framingham, MA, USA"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitzi M.","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Glenn Biggs Institute for Alzheimer\u2019s & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, TX, USA"},{"name":"Department of Neurology, University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia L.","family":"Satizabal","sequence":"additional","affiliation":[{"name":"Glenn Biggs Institute for Alzheimer\u2019s & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, TX, USA"},{"name":"Framingham Heart Study, Framingham, MA, USA"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, MA, USA"},{"name":"Department of Population Health Sciences, University of Texas Health Science Center, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, WA, USA"},{"name":"Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.T.","family":"Longstreth","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Washington, Seattle, WA, USA"},{"name":"Department of Neurology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Bis","sequence":"additional","affiliation":[{"name":"Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Hveem","sequence":"additional","affiliation":[{"name":"HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Levanger, Norway"},{"name":"K. 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