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The most commonly used plasma biomarkers include amyloid-\u03b2 (A\u03b2), phosphorylated tau (p-tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). The extent to which distinct profiles of multiple plasma biomarkers correlate with common neuropathologies is unclear.<\/jats:p>\n                  <jats:p>Using clinicopathologic data from 405 community-dwelling older adults, we applied latent profile analysis to four plasma biomarkers, i.e. A\u03b242\/40 ratio, p-tau217, NfL and GFAP, and examined the correlates of the latent profiles with four degeneration measures: AD, Lewy bodies, limbic-predominant age-related TDP-43 encephalopathy (LATE) and hippocampal sclerosis; and five vascular measures: chronic macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis and arteriosclerosis.<\/jats:p>\n                  <jats:p>On average, participants died at the age of 89, and blood samples for plasma biomarkers were measured 3.9 years before death. Over 75% were female, and 24% were non-Latino Black. We observed three distinct biomarker profiles. Profile 1, characterized by low p-tau217, low GFAP, low NfL and high A\u03b242\/40, represented most participants (55.6%), with better than average biomarker levels. Both Profile 2 and Profile 3 showed worse than average biomarker levels. Profile 2, representing 34.8% of the participants, was high in p-tau217 and GFAP. In contrast, Profile 3, representing 9.6% of the participants, was high in NfL and GFAP. Examination of neuropathologic correlates of these plasma biomarker profiles revealed that Profile 2 exemplifies older adults with a high burden of neurodegeneration; almost all participants (92.9%) in Profile 2 had a diagnosis of pathologic AD, and the group also had the highest percentage of participants with Lewy bodies (41.1%). In comparison, Profile 3 exemplifies older adults with more severe vascular conditions; participants in this group had the highest percentage of macroscopic infarcts (31.6%) and moderate or severe atherosclerosis (42.1%).<\/jats:p>\n                  <jats:p>Together, these findings suggest that common plasma biomarkers may exhibit profiles reflective of distinct pathophysiologic processes.<\/jats:p>","DOI":"10.1093\/brain\/awaf211","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T07:51:52Z","timestamp":1749023512000},"page":"3340-3349","source":"Crossref","is-referenced-by-count":10,"title":["Neuropathologic correlates of distinct plasma biomarker profiles in community-living older adults"],"prefix":"10.1093","volume":"148","author":[{"given":"Lei","family":"Yu","sequence":"first","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Neurological Sciences, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianlian","family":"Du","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Neurological Sciences, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Neurological Sciences, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0072-9817","authenticated-orcid":false,"given":"Lisa L","family":"Barnes","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Neurological Sciences, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L","family":"Dage","sequence":"additional","affiliation":[{"name":"Department of Neurology, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["USA"]},{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen A","family":"Russ","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Foroud","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-554X","authenticated-orcid":false,"given":"David A","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Neurological Sciences, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Schneider","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Neurological Sciences, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Pathology, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A","family":"Boyle","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Psychiatry and Behavioral Sciences, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"2025090219581128200_awaf211-B1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","article-title":"A\/T\/N: An unbiased descriptive classification scheme for Alzheimer disease 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