Effects of obesity on plasma biomarker and amyloid PET trajectories in Alzheimer's disease.

Introduction: Obesity is a risk factor for Alzheimer's disease (AD), but its impact on AD blood biomarker (BBM) and amyloid positron emission tomography (PET) trajectories is unknown.

Methods: One thousand two hundred twenty-eight plasma samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assessed using six leading commercial tests (C2N, Fujirebio, Janssen, ALZpath, Roche, and Quanterix). Amyloid PET scans were used to assess amyloid burden in Centiloids (CLs). Spearman partial correlations assessed cross-sectional associations, while linear mixed-effects models examined the longitudinal impact of obesity status on BBMs and CLs.

Results: Higher body mass index at baseline was correlated with lower levels of plasma phosphorylated tau (p-tau)217, p-tau217 ratio, neurofilament light chain (NfL), glial fibrillary acidic protein, and CLs. However, baseline obesity predicted higher rate of increase in p-tau217, p-tau217 ratio, Roche NfL, and amyloid PET burden over time.

Discussion: This study provides insights for longitudinal changes in AD pathologies, as measured by BBM levels and CLs, in association with obesity.

Highlights: Higher body mass index was related to lower baseline plasma tau phosphorylated at threonine 217 (p-tau217), p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) and amyloid positron emission tomography (PET) burden.Obesity predicts a faster increase in p-tau217, p-tau217 ratio, and NfL.Obesity predicts a faster increase in amyloid PET burden.Changes in GFAP over time are not linked with obesity.