Ozioma Okonkwo, United States of America
University of Wisconsin Wisconsin Alzheimer's Disease Research CenterAuthor Of 1 Presentation
AMYLOID, TAU, AND NEURODEGENERATION CEREBROSPINAL FLUID BIOMARKERS AND LONGITUDINAL COGNITIVE OUTCOMES ACROSS THE ALZHEIMER’S DISEASE CLINICAL SPECTRUM
Abstract
Aims
1) Utilize the NIA-AA research framework to characterize the frequency of cerebrospinal fluid (CSF) amyloid (A) and tau (T) positivity (-/+) across the Alzheimer’s disease (AD) clinical spectrum; 2) among unimpaired A/T groups (A-T-, A-T+, A+T-, A+T+), examine cognitive trajectories and associations with CSF analytes, including candidate biomarkers for neurodegeneration.
Methods
Individuals (N=642) recruited from Wisconsin AD Research Center (WADRC, n=404) and Wisconsin Registry for Alzheimer’s Prevention (WRAP, n=238) studies were assayed using NeuroToolKit (NTK) robust prototype assays (Roche Diagnostics). Differences among A/T groups (demographics, cognition, and NTK markers of degeneration) were assessed using ANOVA or χ2 tests. In subsets unimpaired at baseline (WADRC, n=302; WRAP, n=232), longitudinal PACC-3 performance (Num. assessments, Median[Range]=5[2,9]) across A/T biomarker groups was investigated (linear mixed effects models).
Results
Amyloid positivity (A+) increased with clinical status (unimpaired: 19%, MCI: 63%, dementia: 92%). Among unimpaired (n=533), A+ frequency was higher in subjects aged >65 years and among APOE4+. On NTK measures, unimpaired A/T groups differed on neurodegeneration (4/4 analytes) and glial activation (3/4), but not inflammation (0/1). Neurodegeneration analyte levels were higher in T+ groups; neurogranin demonstrated a stepwise significance pattern of A-T- < A+T- < both A-T+ and A+T+. Although A/T group baseline cognition did not differ, the A+T+ and A+T- groups exhibited faster cognitive decline versus A-T-.
Conclusions
In two separate preclinical cohorts, cognitive decline was evident in A+ biomarker groups. Several NTK analytes, particularly neurogranin, were sensitive to A and/or T positivity indicating that these analytes differ preclinically and require further study.