THE ASSOCIATION OF AGE WITH AΒ, NEUROINFLAMMATION, AND TAU PATHOLOGY USING PET AND PLASMA BIOMARKERS IN LATE-ONSET ALZHEIMER’S DISEASE
- Julie Ottoy, Canada
Abstract
Aims
With the advent of disease-modifying therapeutic trials in early stages of Alzheimer’s disease (AD), disentangling normal age-related biomarker changes from AD-related pathological changes will be crucial to unravel therapy effectiveness in trial populations. Here, we aim to investigate the effects of age, the greatest risk factor of AD, on markers of amyloid-β (Aβ), tau, and neuroinflammation PET in late-onset AD.
Methods
238 participants (120 amyloid- and tau-negative [A-] and 118 amyloid-positive [A+]) from the TRIAD cohort underwent 18F-AZD4694 amyloid-PET and 18F-MK620 tau-PET. A subset also underwent 11C-PBR28 neuroinflammation-PET, plasma Ptau181 and Aβ1-42/Aβ1-40 concentration measures, and 1-year follow-up tau-PET. We investigated the association between age and all PET modalities as well as between age and plasma concentrations using linear regression models, adjusting for sex, education, APOE-ε4, and the remaining PET or plasma variables. In addition, we investigated whether there is a significant difference in these associations between the A- and A+ groups (i.e., interaction-effect age*Aβ-status on PET/plasma biomarkers).
Results
Younger A+ subjects showed increased plasma Ptau181 and tau-PET in Braak3and4 predominant areas at baseline as well as increased tau-PET SUVR changes in Braak1and2 predominant areas after 1-year follow-up compared to older A+ individuals, while there was no age-effect on tau-PET in A-. Second, while we detected a significant main effect of age on neocortical Aβ and orbitofrontal neuroinflammation SUVR, the effect of age on both markers did not significantly differ between A+ and A-.
Conclusions
Future clinical trials should consider age as an important stratification factor particularly when targeting tau in late-onset AD.