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

Background and Objectives To evaluate whether plasma biomarkers of amyloid (A beta 42/A beta 40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups. Methods Individuals 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 epsilon 4 carrier status, and cognitive status. Each participant underwent blood and CSF collection, and amyloid PET was performed in 103 participants (68%). Plasma A beta 42/A beta 40 was measured by a high-performance immunoprecipitation-mass spectrometry assay. Plasma p-tau181, p-tau231, and NfL were measured by Simoa immunoassays. CSF A beta 42/A beta 40 and amyloid PET status were used as primary and secondary reference standards of brain amyloidosis, respectively. Results There 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 epsilon 4 carriers, and 91% were cognitively normal. AA were less likely than NHW participants to have brain amyloidosis by CSF A beta 42/A beta 40 (22% vs 43% positive; p = 0.003). The receiver operating characteristic area under the curve of CSF A beta 42/A beta 40 status with the plasma biomarkers was as follows: A beta 42/A beta 40, 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 A beta 42/A beta 40 status with plasma A beta 42/A beta 40 that included covariates (age, sex, APOE epsilon 4 carrier status, race, and cognitive status), race did not affect the probability of CSF A beta 42/A beta 40 positivity. In similar models based on plasma p-tau181, p-tau231, or NfL, AA participants had a lower probability of CSF A beta 42/A beta 40 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. Discussion Models predicting brain amyloidosis using a high-performance plasma A beta 42/A beta 40 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.

Automated summary

The study aimed to evaluate whether plasma biomarkers detect brain amyloidosis consistently across different racial groups. Results showed that a high-performance plasma A beta 42/A beta 40 assay may provide an accurate measure of brain amyloidosis across African American and non-Hispanic White groups, while models based on plasma p-tau181, p-tau231, and NfL may lead to disproportionate misdiagnosis of African American individuals.