Plasma Alzheimer’s Disease Biomarkers and Brain Amyloid in a Multi‐Ethnic Aging Cohort

Congratulations to Dr. Karen MacFarland, Steven DeKosky, Mellisa Armstrong and David Vaillancourt, on the publication of “Plasma Alzheimer’s Disease Biomarkers and Brian Amyloid in a Multi-Ethnic Aging Cohort,” which appears in the December 2023 issue of Alzheimer’s and Dementia: The Journal of The Alzheimer’s Association.


Background Dementia diagnoses are more common among Hispanic (HW) than non‐Hispanic white (NHW) older adults. Alzheimer’s disease (AD) is the most common neuropathological finding in patients with dementia. Plasma AD biomarkers have accelerated efforts towards increasing access to timely diagnosis, but existing data often come from cohorts lacking ethnic diversity. Clinical translation of plasma AD biomarkers requires continued evaluation in study cohorts that reflect the growing ethnic diversity of the population. Method We studied 379 older adults (age 71.9±7.8 years old, 60.2% female) from the 1Florida Alzheimer’s Disease Research Center who underwent blood draw and analysis for P‐tau181 (Quanterix). Of these, 240 completed Aβ‐PET (converted to Centiloids). Over half (57%) self‐identified as HW (32% Cuba, 18% South American, 7% other). Analyses included 1) comparing plasma biomarker concentrations between clinically normal (CN), amnestic MCI (amnMCI), amnestic dementia (amnDEM), and nonamnestic MCI/dementia (ANCOVA controlling for age), 2) evaluating P‐tau181 correlations with Aβ burden (Spearman’s rho), and 3) determining discriminability (AUC) of Aβ‐PET[+] from Aβ‐PET[‐]. Interactions between independent variables and ethnicity were evaluated to inform whether observed relationships differed between HW and non‐Hispanic white (NHW). Lastly, using a cutoff derived from the PET sub‐cohort, we investigated rates of P‐tau181‐defined “AD positivity” (plasmaAD[+]) between HW and NHW diagnosed with amnMCI. Additional data for plasma GFAP and NfL will also be presented. Results Plasma P‐tau181 was higher in amnMCI (p = .004, d = 0.53) and amnDEM (p<.001, d = 0.97) than CN. Higher P‐tau181 related to greater Aβ burden (ρ = .59 [.50‐.67], p<.001) and had good discriminability between Aβ‐PET[+] and Aβ‐PET[‐] (AUC = 0.86 [0.81‐0.91], Youden’s Index = 2.39 pg/mL). There were no significant interactions with ethnicity. Applying the P‐tau181 cutoff (2.39 pg/mL) to all amnMCI participants, HW diagnosed with amnMCI had lower odds of being plasmaAD[+] than NHW (36.5% vs. 58.5%; OR = 0.41 [0.21‐0.78], p = .006). Conclusion Plasma P‐tau181 may aid etiological diagnosis of cognitively impaired older adults from Hispanic and non‐Hispanic ethnic origins. Hispanic ethnicity alone does not significantly influence the interpretation of how plasma P‐tau181 relates to Aβ‐PET, but may be linked to greater likelihood of non‐AD causes of memory loss. Blood‐based biomarkers could help reduce barriers to clinical diagnosis and research participation that disproportionately impact underrepresented groups.