HAI Book 2025 - Flipbook - Page 363
Moon, Hasom
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Predicting regional Alzheimer9s disease pathology with plasma ptau217 in preclinical AD
Hasom Moon1, Xi Chen1
1
Stony Brook University, Stony Brook, NY, US
Background: Plasma p-tau217 is recognized as a promising biomarker with high sensitivity and specificity for
detecting Alzheimer9s disease (AD). However, its value in inferring regional and longitudinal AD pathology is largely
unstudied. This study aimed to examine how plasma p-tau217 can reflect regional tau burden and longitudinal
change, in comparison to A´, in PET.
Methods: Using data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer9s disease (A4) study, 333 A´+
cognitively unimpaired older adults (age g 65 years, 190 Females) underwent repeated 18-F Florbetapir A´ PET and
18-F Flortaucipir tau PET, with baseline plasma p-tau217 measured using an Eli Lilly electrochemiluminescence
immunoassay. Associations between p-tau217 and regional SUVRs were examined using correlations with
Bonferroni correction.
Results: Plasma p-tau217 was associated with concurrent tau in early-to-mid Braak regions, primarily restricted
to temporal-parietal regions and precuneus (Figure 1a-b) and A´ burden across cortical regions, particularly in
precuneus (Figure 2a-b). When predicting tau PET distribution using a single measure of p-tau217, we found the
predicted tau burden was largely similar to the observed pattern (Figure 3). Longitudinally, baseline plasma ptau217 predicted tau accumulation across broader cortical regions (Figure 1c-d), extending beyond temporal
regions further to medial-lateral frontal regions. However, plasma p-tau217 had little prediction for A´ change
(Figure 2c-d), probably reflecting A´ plateau in late preclinical AD.
Conclusion: We found evidence highlighting the potential of using a single measurement of plasma p-tau217 to
infer regional pathology burden in preclinical AD. Plasma p-tau217 reflects concurrent tau pathology in temporalparietal regions and cortical amyloid burden. Furthermore, its strong prediction for future tau accumulation, but
not A´, suggests that elevation of p-tau217 may be an earlier event reflecting emerging tau pathology prior to
measurable PET changes, offering support for clinical utility of plasma p-tau217 for disease monitoring, early
detection, and timely intervention of AD.
HAI2025 - 363
