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Comparison of plasma and CSF biomarkers across ethnoracial groups in the ADNI

Abstract Introduction Ethnoracial differences in cerebrospinal fluid (CSF; amyloid beta 42 [Aβ42], total tau [t‐tau], phosphorylated tau 181 [p‐tau181], and plasma (p‐tau181, neurofilament light [NfL]) biomarkers of Alzheimer's disease (AD) are incompletely understood. Methods We performed cross‐sectional analyses with and without adjustment for covariates comparing baseline CSF (Aβ42, t‐tau, p‐tau181) and plasma (p‐tau181, NfL) values in 47 African Americans (AAs) matched to 141 non‐Hispanic Whites (NHWs) and 43 Latinos (LAs) matched to 129 NHWs from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results Unadjusted comparisons revealed no significant differences in plasma or CSF biomarkers between AAs and NHWs. A trend toward a lower CSF t‐tau and p‐tau181 in LAs compared to NHWs was observed, without significant differences in plasma biomarkers. After adjusting for covariates, there were no significant differences in CSF or plasma biomarkers between AAs and NHWs or between LAs and NHWs. Discussion Plasma and CSF AD biomarkers may perform similarly across diverse populations but future studies in large, diverse cohorts are needed.


INTRODUCTION
Fluid biomarkers of Alzheimer's disease (AD) (ie, amyloid beta [Aβ], tau) and neurodegeneration (ie, neurofilament light [NfL]) are understudied in diverse populations yet represent important diagnostic tools due to their accessibility. Ethnoracial differences in biomarker concentrations across the disease spectrum must be better understood, as African American (AA) and Latino (LA) individuals will be disproportionately affected by AD and related disorders in the coming decades. 1 Validating biomarkers in diverse populations is also essential when considering implementation of the 2018 NIA-AA (National Institute on Aging-Alzheimer's Association) Research Framework for AD 2 and selecting appropriate candidates for emerging molecular therapies. 3 Direct comparisons of fluid biomarkers between ethnoracial groups have been limited and have yielded mixed results, although lower concentrations of cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau 181 (p-tau181) among AAs compared to non-Hispanic Whites (NHWs) have been reported. [4][5][6][7] Novel AD plasma biomarkers are less studied among diverse groups. Mixed results, including an effect of race and ethnicity on plasma t-tau, as well as no impact of race or ethnicity on biomarker concentrations have been reported. [8][9][10][11][12] Prior studies have largely included cognitively normal participants from single sites and have not fully characterized social determinants of health (eg, educational background, socioeconomic background) among participants.
We leveraged data available through the Alzheimer's Disease Neuroimaging Initiative (ADNI) to study ethnoracial differences in plasma (p-tau181, NfL) and CSF (Aβ42, t-tau, p-tau181) biomarkers among AA, NHW, and LA individuals, adjusting for sociodemographic factors and comorbidities. Based on the previous literature, we hypothesized significantly lower CSF t-tau and plasma and CSF p-tau181 concentrations among AA and LA individuals compared to NHWs, but similar NfL levels among AAs and LAs compared to NHWs.

RESULTS
Baseline demographic and clinical data of matched groups are noted in Table 1.
Unadjusted comparisons between LAs and NHWs revealed no significant differences in plasma NfL (pFDR = 1) and p-tau181 (pFDR = .9) measures or CSF Aβ42 (pFDR = 1) ( Figure 1B,  Figure 1B, Table   S1). There were no significant differences in total white matter hyper-intensity volume (pFDR = 0.73) ( Figure 1C, Table S1). In the multiple regression model adjusting for covariates, LAs no longer had signifi-  Our study is unique in that it includes data from the ADNI, a large study inclusive of over 60 sites in the United States and Canada. Previous studies have largely been limited to a single site or a small number of sites. We included a wide range of impairment levels and did not limit to the cognitively unimpaired. We had data from both sexes.
We employed a matching strategy to match for multiple sociodemographic and clinical variables that may have differed between ethnoracial groups. We also included measurements of white matter pathology in addition to fluid biomarker data. There is no biological basis for racial and ethnic categories, and our findings suggest that ethnoracial no interaction between ethnicity and plasma p-tau or NfL. 9 Barker 11 found no impact of ethnicity on plasma NfL among 309 individuals with varying impairment from a single Alzheimer's Disease Research Center (ADRC) with significant Latino representation. This is consistent with findings from a study comparing 890 Mexican Americans and 813 NHWs, although there were significant differences in plasma ttau between groups. 12 Finally, Brickman 10