Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light

Suzanne E. Schindler, Thomas K. Karikari, Nicholas J. Ashton, Rachel L. Henson, Kevin E. Yarasheski, Tim West, Mathew R. Meyer, Kristopher M. Kirmess, Yan Li, Benjamin Saef, Krista L. Moulder, David Bradford, Anne M. Fagan, Brian A. Gordon, Tammie L.S. Benzinger, Joyce Balls-Berry, Randall J. Bateman, Chengjie Xiong, Henrik Zetterberg, Kaj BlennowJohn C. Morris

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Background and ObjectivesTo evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-Tau181 and p-Tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.MethodsIndividuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age, APOE ϵ4 carrier status, and cognitive status. Each participant underwent blood and CSF collection, and amyloid PET was performed in 103 participants (68%). Plasma Aβ42/Aβ40 was measured by a high-performance immunoprecipitation-mass spectrometry assay. Plasma p-Tau181, p-Tau231, and NfL were measured by Simoa immunoassays. CSF Aβ42/Aβ40 and amyloid PET status were used as primary and secondary reference standards of brain amyloidosis, respectively.ResultsThere were 76 matched pairs of AA and NHW participants (n = 152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were APOE ϵ4 carriers, and 91% were cognitively normal. AA were less likely than NHW participants to have brain amyloidosis by CSF Aβ42/Aβ40 (22% vs 43% positive; p = 0.003). The receiver operating characteristic area under the curve of CSF Aβ42/Aβ40 status with the plasma biomarkers was as follows: Aβ42/Aβ40, 0.86 (95% CI 0.79-0.92); p-Tau181, 0.76 (0.68-0.84); p-Tau231, 0.69 (0.60-0.78); and NfL, 0.64 (0.55-0.73). In models predicting CSF Aβ42/Aβ40 status with plasma Aβ42/Aβ40 that included covariates (age, sex, APOE ϵ4 carrier status, race, and cognitive status), race did not affect the probability of CSF Aβ42/Aβ40 positivity. In similar models based on plasma p-Tau181, p-Tau231, or NfL, AA participants had a lower probability of CSF Aβ42/Aβ40 positivity (odds ratio 0.31 [95% CI 0.13-0.73], 0.30 [0.13-0.71], and 0.27 [0.12-0.64], respectively). Models of amyloid PET status yielded similar findings.DiscussionModels predicting brain amyloidosis using a high-performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-Tau181, p-Tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA individuals.

Original languageEnglish
Pages (from-to)E245-E257
Issue number3
StatePublished - Jul 19 2022


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