Differences between high‐precision Alzheimer’s disease plasma and PET biomarkers among cognitively normal older Black and White adults

Abstract Background We evaluated whether baseline differences existed in various plasma Alzheimer’s disease (AD) biomarkers in cognitively normal participants racialized as Black or White. Method This cross‐sectional study included 203 (n = 83 non‐Hispanic Black [NHB] and n = 120 non‐Hispanic White [NHW]) cognitively unimpaired older adults from the NYU Alzheimer’s Disease Research Center. Of the 203, 115 (39NHB, 76 NHW) had tau‐PET (PI‐2620/MK‐6240) data; 195 (85 NHB, 110 NHW) had amyloid‐PET (florbetaben); 98 (39 NHB, 59 NHW) had plasma Aß40 and Ab42 data, 93 (37 NHB, 56 NHW) had data for total tau, 135 (55 NHB, 80 NHW) had neurofilament light (NfL) and glial fibrillary protein (GFAP) data and 139 (57 NHB, 82 NHW) had pTau181 data. Plasma biomarkers assay Aß 40, Aß42, total tau [t‐tau], neurofilament light [NfL], glial fibrillary acid protein [GFAP], ubiquitin carboxyl‐terminal hydrolase L1 [UCH‐L1] and pTau181 were measured were measured using Quanterix SIMOA HD‐1. Result Overall, mean (SD) age was 75.6 (6.5) NHW vs. 68.9 NHB (p = .008), BMI was 27.4 (9.7) vs. 32.4 (11.2) (p = .161), and education 17.0 (2.1) vs. 16.4 (2.32) (p = .273) for NHW vs. NHB respectively. Overall, 135 (66.5%) were females, of which 61 (73.5%) were NHB, and 62 were APOE e4 carriers [30.5%], of which 27 were NHB. Compared to NHW, NHB subjects had significantly lower plasma Aß40 (One‐tailed t‐test p = .006), NfL levels (p = .0005), Tau (p = .0313), pTau181 (p = .0015), and GFAP (p = .0005). NHB subjects had lower amyloid‐PET SUVR levels compared to NHW subjects (p = .0014). Baseline plasma Aß42/40 and pTau181/Aß42 levels were higher in NHB versus NHW participants (p = .002), consistent lower levels of amyloid pathology in NHB participants. There were no significant differences in levels of plasma Aß42, tau‐PET SUVR, and UCH‐L1. Conclusion In this sample of cognitively normal older adults, NHB participants had biomarker measures suggestive of lower levels of cerebral amyloid pathology. This warrants further correlation with brain imaging and cognitive outcomes, and examination of the potential impact of demographic, socio‐structural and genetic factors on observed differences. Additionally, this may imply that racial variability in amyloid threshold possibly exists before clinical AD onset, potentially lowering the proportion of NHB patients eligible for AD therapies and trials.