Cluster analysis of the longitudinal progression of plasma biomarkers and amyloid imaging in the Wisconsin Registry for Alzheimer’s Prevention

Abstract

AbstractBackgroundThe analysis of the longitudinal progression of plasma biomarkers and amyloid imaging might lead to new insights in the early pattern of biomarker changes.MethodPlasma Aß42/Aß40, pTau231/Aß42, pTau181/Aß42, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) were measured for n = 223 subjects and 1673 total visits in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) using Quanterix Simoa assays at the University of Gothenburg. Global distribution volume ratio (DVR) was computed from 11C‐Pittsburgh compound B PET scans. Inclusion criteria included Amyloid or CSF Amyloid positive status, and at least one plasma serial value. Trajectories spanning age 46.9 to 80.3 years old for the DVR and plasma biomarkers were estimated by fitting a vector field to the longitudinal data (https://arxiv.org/abs/2206.15215). A Louvain community clustering analysis was performed. The time from Amyloid positivity (DVR = 1.19; centiloid of 22) was also computed for all individual trajectories that crossed this threshold.ResultThe Louvain community clustering algorithm resulted in three distinct communities (Fig 1): no increase in DVR or plasma biomarkers (Green, n = 88(39.5%)); increase in DVR and all plasma biomarkers except NFL (Red, 41(18.4%)); and mixed DVR plus GFAP and NFL increase (Blue, 94(42.2%)). Time since Amyloid positivity (TSAP) was computed for the subset of subjects (n = 84) expected to cross the Amyloid positivity threshold. The Louvain communities as a function of TSAP are shown in Fig 2.ConclusionWe identified three communities regarding the longitudinal progression of amyloid PET and plasma biomarker levels. Plasma biomarkers were dynamic up to 30 years before Amyloid positivity.