HAI Book 2025 - Flipbook - Page 151
Gogola, Alexandra
21
Plasma Aβ as predictor of Aβ accumulation in non-demented
participants
Alexandra Gogola1, Ann Cohen2, Brian Lopresti1, Beth Snitz3, Milos Ikonomovic4,5, Dana
Tudorascu2, Davneet Minhas1, Julia Kofler5, Cristy Matan1, Howard Aizentein2, Oscar Lopez3,
Thomas Karikari2, Victor Villemagne2
1
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, US
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, US
3
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, US
4
Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, US
5
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, US
2
Background: Given the increasing use of plasma biomarkers for Alzheimer9s disease (AD) studies, it is necessary
to better understand the associations of plasma and PET biomarkers of ´-amyloid (A´) in relation to A´
accumulation and conversion from PET A- to A+.
Methods: We evaluated 58 non-demented participants (31 cognitively unimpaired (CU), 27 MCI) from ADNI who had
plasma A´42 and A´40 outcomes and longitudinal Centiloid values. All participants were PET A- at baseline.
Participants were split into infra- and suprathreshold groups with a cutoff of 20 CL. Plasma A´42/40 values,
analyzed through the C2N mass spectrometry-based assay, were split based on a value of 0.13. Kaplan-Meyer
survival and Cox proportional models, accounting for baseline Centiloids, sex, age, and APOE*4 status, evaluated
the association of plasma A´42/40 status with risk of conversion to PET A+. Linear regression models, adjusting
for the same covariates, assessed the association of plasma A´42/40 and Centiloid values with A´ accumulation
(CL/yr).
Results: Kaplan-Meyer survival analysis results showed that plasma A´ status distinctly differentiates PET Atrajectories, predicting conversion to A+ in ~6 years. Cox proportional models found that while categorical plasma
A´42/40 was not significantly associated with conversion to A+ (p=0.111), it had the largest hazard ratio within the
model (8.69). Linear regression models of the continuous measures revealed that plasma A´42/40 was
significantly associated (all non-demented: b=-142.29, p=0.002; CU-only: b=-162.85, p=0.008) with A´
accumulation.
Conclusions: The models suggest that plasma Ab in PET A- participants predicts A´ accumulation, and eventual
conversion from A- to A+. This follows the notion that soluble A´, measured in plasma or CSF, becomes abnormal
before insoluble A´ measured with PET does. Therefore, plasma A´-positive, A´-PET negative identify individuals
at the very early stages of A´ accumulation, at risk of progression, and likely to benefit the most from anti-A´
therapy.
HAI2025 - 151
