Abstract
Alzheimers Dement. 2025 Dec;21 Suppl 2:e101237. doi: 10.1002/alz70856_101237.
ABSTRACT
BACKGROUND: Plasma pTau217 is a robust indicator of amyloid pathology recently included as a Core 1 biomarker for Alzheimer's disease (AD). However, factors like body mass can influence its measurement. Investigation of how much this impacts classification of participants as Core 1 A+ is relevant for studies looking at early AD stages. In this work, we assess the effect of corpulence on concentrations of plasma pTau217 and other biomarkers.
METHOD: We analyzed longitudinal plasma samples from 746 participants in the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center with recent PET-PiB and PET-MK6240 data (max 1.5 years before last plasma sample). We measured five blood biomarkers (pTau217-ALZpath, GFAP, NfL, Aβ40, and Aβ42) using the Quanterix HD-X platform. Amyloid onset age was estimated using the sampled iterative local approximation algorithm (SILA) on PET-PiB uptake values (locally-derived Amyloid+ threshold ∼17 Centiloids). We modeled biomarker levels using mixed gamma regression; terms included age, corpulence, APOEε4 carriage, and sex. For pTau217, we modeled amyloid non-accumulators and accumulators separately, using SILA-chronicity instead of age in the latter. An ROC analysis was used to assess pTau217 classification performance against PET-PiB visual reads on the subset that was also tau negative via PET-MK6240 visual read.
RESULT: Most participants were cognitively unimpaired at first plasma sample. (697, 93.4%; 511 females; 39.4-93.8 yo, mean(SD) age=65.7(7.7)). The ROC-determined pTau217 threshold was 0.42 pg/mL (Figure 1; AUC(CI)=0.84 (0.8-0.89). Everypoint increase in corpulence (centered at 13, regular corpulence) was associated with a 4-5% reduction in pTau217 levels in both amyloid accumulators (β(CI)=0.95(0.92-0.97), p <.001) and non-accumulators (β(CI)=0.96(0.94-0.98), p <.001). For amyloid accumulators, this represents ∼3.25 years of delay to reach the ROC threshold among individuals with obesity (corpulence=21). This reduction was also present in concentrations of GFAP (β=0.96, CI=0.94-0.97, p <.001) and NfL (β=0.96, CI=0.94-0.97, p <.001) but not detected in the Aβ42/Aβ40 ratio (p = .550).
CONCLUSION: Our results show that corpulence, a body mass measure, is associated with plasma biomarker levels. Accounting for corpulence might lead to significant improvements in plasma-based early detection of AD.
PMID:41442511 | DOI:10.1002/alz70856_101237
UK DRI Authors
