{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:36:07Z","timestamp":1792859767044,"version":"4.5.0"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Differences in cerebrospinal fluid (CSF) tau Alzheimer dementia (AD) biomarkers by self-identified race have been observed in prior studies. More recently, plasma biomarkers have been gaining recognition, but whether they exhibit similar differences is unclear. Furthermore, the underlying explanation for these differences in AD biomarkers is still unexplored.<\/jats:p><\/jats:sec>Objectives<\/jats:title>To investigate differences in plasma biomarkers by race and genetic ancestry and explore potential underlying explanations for these differences.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This cross-sectional study used participant data from the Brain, Stress, Hypertension, and Aging Research Program (B-SHARP), an observational study conducted in the greater Atlanta metropolitan area. Participants were enrolled from March 1, 2016, to January 1, 2020.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Main outcomes were plasma and CSF amyloid-\u03b2 (A\u03b2) 42, A\u03b240, phosphorylated tau181<\/jats:sub> (p-tau181<\/jats:sub>), and neurofilament light. General linear models were used for key comparisons.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Main independent variables were self-identified race and genetic ancestry. Additional variables were cardiovascular factors, APOE4<\/jats:italic>, educational attainment, Area Deprivation Index, and C-reactive protein (reflecting systemic inflammation state).<\/jats:p><\/jats:sec>Results<\/jats:title>This analysis included 617 participants (mean [SD] age, 66 [7.9] years; 300 [49%] African American and 317 [51%] White; 429 [70%] with mild cognitive impairment). On the basis of self-reported race, plasma levels of A\u03b242 (adjusted mean difference, \u22121.20 pg\/mL; 95% CI, \u22122.33 to \u22120.07 pg\/mL), A\u03b240 (adjusted mean difference, \u221237.78 pg\/mL; 95% CI, \u221260.16 to \u221215.39 pg\/mL), p-tau181<\/jats:sub> (adjusted mean difference, \u22124.66 pg\/mL; 95% CI, \u22127.05 to \u22121.90 pg\/mL), and neurofilament light (adjusted mean difference, \u22121.58; 95% CI, \u22122.83 to \u22120.19 pg\/mL) were consistently lower in African American individuals after adjusting for demographic characteristics, educational attainment, cognition, APOE4<\/jats:italic>, and cardiovascular factors. A similar pattern was observed in the CSF biomarkers except for A\u03b242 and A\u03b240. Although unadjusted analyses revealed an association between these biomarkers and African ancestry, these associations were not significant after adjusting for the same covariates. Differences by self-reported race were not explained by varied cardiovascular risk factors, C-reactive protein, educational attainment, or Area Deprivation Index.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cross-sectional study of plasma biomarkers by race and genetic ancestry, the results indicated that plasma p-tau181<\/jats:sub>, A\u03b240, and NFL were lower in African American individuals based on self-reported race but not genetic ancestry. These differences were not explained by cardiovascular risks or clinical stage differences. These racial differences should be considered in clinical interpretations and clinical trial screenings to avoid an additional increase in underrepresentation of African American individuals in AD trials.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.35068","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T15:39:50Z","timestamp":1665070790000},"page":"e2235068","source":"Crossref","is-referenced-by-count":79,"title":["Association of Plasma and Cerebrospinal Fluid Alzheimer Disease Biomarkers With Race and the Role of Genetic Ancestry, Vascular Comorbidities, and Neighborhood Factors"],"prefix":"10.1001","volume":"5","author":[{"given":"Ihab","family":"Hajjar","sequence":"first","affiliation":[{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, Georgia"},{"name":"Department of Neurology, University of Texas Southwestern, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Okafor","sequence":"additional","affiliation":[{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Waligorska","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia"},{"name":"Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia C.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia"},{"name":"Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"issue":"4","key":"zoi220997r1","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1002\/ana.v63:4","article-title":"Frequency and course of mild cognitive impairment in a multiethnic community.","volume":"63","author":"Manly","year":"2008","journal-title":"Ann Neurol"},{"issue":"5","key":"zoi220997r2","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1097\/JGP.0b013e3181f7d881","article-title":"Ethnoracial differences in the clinical characteristics of Alzheimer\u2019s disease at initial presentation at an urban Alzheimer\u2019s disease center.","volume":"19","author":"Livney","year":"2011","journal-title":"Am J Geriatr Psychiatry"},{"issue":"11","key":"zoi220997r3","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1097\/00019442-200511000-00006","article-title":"Racial differences in the progression of cognitive decline in Alzheimer disease.","volume":"13","author":"Barnes","year":"2005","journal-title":"Am J Geriatr Psychiatry"},{"issue":"1","key":"zoi220997r4","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s13195-017-0315-1","article-title":"Race modifies the relationship between cognition and Alzheimer\u2019s disease cerebrospinal fluid biomarkers.","volume":"9","author":"Howell","year":"2017","journal-title":"Alzheimers Res Ther"},{"issue":"5","key":"zoi220997r5","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1212\/WNL.0000000000002914","article-title":"The ARIC-PET amyloid imaging study: brain amyloid differences by age, race, sex, and APOE.","volume":"87","author":"Gottesman","year":"2016","journal-title":"Neurology"},{"issue":"3","key":"zoi220997r6","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1001\/jamaneurol.2018.4249","article-title":"Assessment of racial disparities in biomarkers for Alzheimer disease.","volume":"76","author":"Morris","year":"2019","journal-title":"JAMA Neurol"},{"issue":"12","key":"zoi220997r7","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.17363","article-title":"Racial disparity in cerebrospinal fluid amyloid and tau biomarkers and associated cutoffs for mild cognitive impairment.","volume":"2","author":"Garrett","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"12","key":"zoi220997r8","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1001\/jamaneurol.2017.2712","article-title":"Interpreting biomarker results in individual patients with mild cognitive impairment in the Alzheimer\u2019s Biomarkers in Daily Practice (ABIDE) project.","volume":"74","author":"van Maurik","year":"2017","journal-title":"JAMA Neurol"},{"issue":"1","key":"zoi220997r9","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1038\/s41467-021-23746-0","article-title":"Plasma biomarkers of Alzheimer\u2019s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations.","volume":"12","author":"Cullen","year":"2021","journal-title":"Nat Commun"},{"issue":"9","key":"zoi220997r10","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1001\/jamaneurol.2019.1632","article-title":"Performance of fully automated plasma assays as screening tests for Alzheimer disease-related \u00df-amyloid status.","volume":"76","author":"Palmqvist","year":"2019","journal-title":"JAMA Neurol"},{"issue":"5","key":"zoi220997r11","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/S1474-4422(20)30071-5","article-title":"Blood phosphorylated tau 181 as a biomarker for Alzheimer\u2019s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts.","volume":"19","author":"Karikari","year":"2020","journal-title":"Lancet Neurol"},{"issue":"3","key":"zoi220997r12","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s41591-020-0755-1","article-title":"Plasma P-tau181 in Alzheimer\u2019s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer\u2019s dementia.","volume":"26","author":"Janelidze","year":"2020","journal-title":"Nat Med"},{"issue":"11","key":"zoi220997r13","doi-asserted-by":"publisher","first-page":"3234","DOI":"10.1093\/brain\/awaa286","article-title":"Longitudinal plasma p-tau217 is increased in early stages of Alzheimer\u2019s disease.","volume":"143","author":"Mattsson-Carlgren","year":"2020","journal-title":"Brain"},{"issue":"12","key":"zoi220997r14","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911170","article-title":"Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer\u2019s disease.","volume":"11","author":"Palmqvist","year":"2019","journal-title":"EMBO Mol Med"},{"issue":"7","key":"zoi220997r15","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1001\/jamaneurol.2019.0765","article-title":"Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease.","volume":"76","author":"Mattsson","year":"2019","journal-title":"JAMA Neurol"},{"issue":"4","key":"zoi220997r16","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease.","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement"},{"key":"zoi220997r17","doi-asserted-by":"publisher","first-page":"f7051","DOI":"10.1136\/bmj.f7051","article-title":"Effect of socioeconomic disparities on incidence of dementia among biracial older adults: prospective study.","volume":"347","author":"Yaffe","year":"2013","journal-title":"BMJ"},{"issue":"4","key":"zoi220997r18","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1037\/pag0000032","article-title":"Effects of education and race on cognitive decline: an integrative study of generalizability versus study-specific results.","volume":"30","author":"Gross","year":"2015","journal-title":"Psychol Aging"},{"issue":"5","key":"zoi220997r19","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1056\/NEJMms2029562","article-title":"Race and genetic ancestry in medicine\u2014a time for reckoning with racism.","volume":"384","author":"Borrell","year":"2021","journal-title":"N Engl J Med"},{"issue":"1","key":"zoi220997r20","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s13195-021-00855-y","article-title":"Race, APOE genotypes, and cognitive decline among middle-aged urban adults.","volume":"13","author":"Beydoun","year":"2021","journal-title":"Alzheimer Res Therapy"},{"issue":"2","key":"zoi220997r21","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/ana.v89.2","article-title":"Socioeconomic status mediates racial differences seen using the AT(N) Framework.","volume":"89","author":"Meeker","year":"2021","journal-title":"Ann Neurol"},{"issue":"1","key":"zoi220997r22","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.v6.1","article-title":"The Area Deprivation Index: a novel tool for harmonizable risk assessment in Alzheimer\u2019s disease research.","volume":"6","author":"Zuelsdorff","year":"2020","journal-title":"Alzheimers Dement (N Y)"},{"key":"zoi220997r23","doi-asserted-by":"publisher","DOI":"10.1007\/s40615-022-01238-1","article-title":"The effects of race\/ethnicity, age, and area deprivation index (ADI) on COVID-19 disease early dynamics: Washington, D.C. case study.","author":"Adjei-Fremah","year":"2022","journal-title":"J Racial Ethn Health Disparities"},{"key":"zoi220997r24","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.avsg.2021.03.037","article-title":"Area deprivation index score is associated with lower rates of long term follow-up after upper extremity vascular injuries.","volume":"75","author":"Boutrous","year":"2021","journal-title":"Ann Vasc Surg"},{"issue":"5","key":"zoi220997r25","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1097\/HCR.0000000000000591","article-title":"Area deprivation index and cardiovascular events: can cardiac rehabilitation mitigate the effects?","volume":"41","author":"Guhl","year":"2021","journal-title":"J Cardiopulm Rehabil Prev"},{"issue":"11","key":"zoi220997r26","doi-asserted-by":"publisher","first-page":"867","DOI":"10.2471\/BLT.07.045120","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"85","author":"von Elm","year":"2007","journal-title":"Bull World Health Organ"},{"issue":"12","key":"zoi220997r27","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1001\/archneurol.2010.301","article-title":"Validation of consensus panel diagnosis in dementia.","volume":"67","author":"Gabel","year":"2010","journal-title":"Arch Neurol"},{"issue":"4","key":"zoi220997r28","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/jgs.2005.53.issue-4","article-title":"The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc"},{"key":"zoi220997r29","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1192\/bjp.140.6.566","article-title":"A new clinical scale for the staging of dementia.","volume":"140","author":"Hughes","year":"1982","journal-title":"Br J Psychiatry"},{"issue":"3","key":"zoi220997r30","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1093\/geronj\/37.3.323","article-title":"Measurement of functional activities in older adults in the community.","volume":"37","author":"Pfeffer","year":"1982","journal-title":"J Gerontol"},{"issue":"8","key":"zoi220997r32","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1093\/arclin\/acu059","article-title":"Quality of education predicts performance on the Wide Range Achievement Test-4th Edition Word Reading subtest.","volume":"29","author":"Sayegh","year":"2014","journal-title":"Arch Clin Neuropsychol"},{"issue":"6","key":"zoi220997r33","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.1002\/hbm.v39.6","article-title":"A comparison of manual tracing and FreeSurfer for estimating hippocampal volume over the adult lifespan.","volume":"39","author":"Schmidt","year":"2018","journal-title":"Hum Brain Mapp"},{"issue":"5","key":"zoi220997r34","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s00401-011-0808-0","article-title":"Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI.","volume":"121","author":"Shaw","year":"2011","journal-title":"Acta Neuropathol"},{"issue":"9","key":"zoi220997r35","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1101\/gr.094052.109","article-title":"Fast model-based estimation of ancestry in unrelated individuals.","volume":"19","author":"Alexander","year":"2009","journal-title":"Genome Res"},{"issue":"6","key":"zoi220997r36","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1080\/10705511.2020.1777133","article-title":"Causal mediation programs in R, Mplus, SAS, SPSS, and Stata.","volume":"27","author":"Valente","year":"2020","journal-title":"Struct Equ Modeling"},{"issue":"8","key":"zoi220997r37","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1002\/alz.v17.8","article-title":"Plasma p-tau181, p-tau217, and other blood-based Alzheimer\u2019s disease biomarkers in a multi-ethnic, community study.","volume":"17","author":"Brickman","year":"2021","journal-title":"Alzheimers Dement"},{"key":"zoi220997r38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2020.117270","article-title":"Comparing fluid biomarkers of Alzheimer\u2019s disease between African American or Black African and white groups: a systematic review and meta-analysis.","volume":"421","author":"Chaudhry","year":"2021","journal-title":"J Neurol Sci"},{"issue":"1","key":"zoi220997r39","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1001\/jamaneurol.2015.3037","article-title":"Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression.","volume":"73","author":"Zetterberg","year":"2016","journal-title":"JAMA Neurol"},{"issue":"2","key":"zoi220997r40","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000571","article-title":"African Americans have differences in CSF soluble TREM2 and associated genetic variants.","volume":"7","author":"Schindler","year":"2021","journal-title":"Neurol Genet"},{"key":"zoi220997r31","volume-title":"Neuropsychological Assessment","author":"Lezak","year":"2012","edition":"5th ed"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2797044\/hajjar_2022_oi_220997_1664303851.08078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T15:39:53Z","timestamp":1665070793000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2797044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,6]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10,3]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.35068","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,6]]}}}