TY - JOUR
T1 - Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light
AU - Schindler, Suzanne E.
AU - Karikari, Thomas K.
AU - Ashton, Nicholas J.
AU - Henson, Rachel L.
AU - Yarasheski, Kevin E.
AU - West, Tim
AU - Meyer, Mathew R.
AU - Kirmess, Kristopher M.
AU - Li, Yan
AU - Saef, Benjamin
AU - Moulder, Krista L.
AU - Bradford, David
AU - Fagan, Anne M.
AU - Gordon, Brian A.
AU - Benzinger, Tammie L.S.
AU - Balls-Berry, Joyce
AU - Bateman, Randall J.
AU - Xiong, Chengjie
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Morris, John C.
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2022/7/19
Y1 - 2022/7/19
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000200358
DO - 10.1212/WNL.0000000000200358
M3 - Article
C2 - 35450967
AN - SCOPUS:85130307027
SN - 0028-3878
VL - 99
SP - E245-E257
JO - Neurology
JF - Neurology
IS - 3
ER -