Differential A/T/N Networks of Cerebrospinal Fluid and Neuroimaging Biomarkers and their Prediction of Cognition between Self‐reported Black/African American and Non‐Hispanic White Individuals
Authors: Xiong Chengjie , Lu Ruijin , Lah James J. , Wolk David A. , Gleason Carey E. , Roberson Erik D , Schindler Suzanne E. , Benzinger Tammie L.S. , Shaw Les M , Manzanares Cecelia , Qiu Deqiang , Hassenstab Jason J. , Moulder Krista L. , Balls‐Berry Joyce E , Sperling Reisa A. , Johnson Keith A. , Levey Allan I. , Johnson Sterling C , Gremminger Emily , Agboola Folasade , Grant Elizabeth A , Hornbeck Russ C. , Massoumzadeh Parinaz , Keefe Sarah J. , Dierker Donna , Gray Julia D , Henson Rachel L. , Streitz Marissa , Mechanic‐Hamilton Dawn , Stites Shana D. , Morris John C 
Published: December 2023

Background

Differences in absolute levels of individual biomarkers from cerebrospinal fluid (CSF), amyloid PET, and MRI imaging between self‐reported Black and White individuals were reported. How the A/T/N network of AD biomarkers is biologically connected within a racialized group and whether it predicts cognition differentially between groups remain unknown.

Method

The Study of Race to Understand Alzheimer Biomarkers(SORTOUT‐AB) has centrally re‐processed the CSF samples and imaging scans collected at four AD Research Centers/studies: Washington University, University of Pennsylvania, Emory University, and the Harvard Aging Brain Study. A total of 286 Black and 2080 White participants had CSF biomarker data, 157 Black and 936 White participants provided PET amyloid biomarker data, 322 Black and 1530 White individuals had MRI structural data, and 67 Black and 492 White participants provided PET Tau biomarker data. Spearman correlations across biomarkers and cognition/memory were estimated within each race, then compared between groups, adjusting for age, sex, APOE ε4 status, dementia status, and education.

Results

The absolute correlation between CSF Aβ42 and the centiloid scale of PET amyloid mean cortical SUVR was significantly larger in White(r = ‐0.45) versus Black(r = ‐0.04) participants, similar to the absolute correlations between Aβ42/40 ratio and each of below: PET amyloid centiloid(White r = ‐0.61, Black r = ‐0.12), CSF Tau(White r = ‐0.43, Black r = ‐0.25), and CSF pTau181(White r = ‐0.54, Black r = ‐0.33). Aβ42 alone did not correlate with Tau or pTau181 in White individuals, but positively correlated with Tau(r = 0.15) and pTau181(r = 0.16) in Black participants. Significantly larger positive correlations were observed in Black versus White individuals between CSF Aβ40 and pTau181(Black r = 0.68, White r = 0.55). PET amyloid centiloid, MRI hippocampal volume, and cortical thickness all predicted cognition, with no racial differences observed. However, cognition/memory was better predicted by Aβ42/40 for White verses Black participants(Black r = 0.07, White r = 0.22), Tau(Black r = ‐0.06, White r = ‐0.20), and pTau181(Black r = ‐0.02, White r = ‐0.23).

Conclusion

Biological associations of CSF and imaging biomarkers differed between Black and White groups, suggesting that current A/T/N research framework of AD biomarkers may not apply across racialized groups. The prediction of CSF biomarkers to cognition also differed between groups. Use of biomarkers in studying AD and designing/analyzing AD clinical trials must appropriately address racial differences.