Early functional changes and plasma GFAP in Swedish families with Autosomal Dominant Alzheimer’s disease mutations

Abstract

<p>We aimed to understand longitudinal associations between Alzheimer’s disease (AD) biomarkers in Autosomal Dominant AD (ADAD) across estimated years to symptom onset (EYO). Forty-five individuals (19 mutation carriers [EYO = −7.9 ± 11.7 years, <em>APP</em> N = 11; <em>PSEN1</em> N = 8]) from Swedish ADAD families participated. All received baseline 18F-Flurodeoxyglucose (FDG) PET and cognitive testing, and a subset (N = 26) plasma glial fibrillary acidic protein (GFAP) measurement. Follow-up data collection (including 106 FDG scans) was performed over 7.4 ± 6.4 years (visits ranged from 1–5, EYO = −25.8 to +10.3 years in mutation carriers). Mixed effects models were applied to determine longitudinal associations. <em>APP</em> and <em>PSEN1</em> mutation carriers showed different FDG uptake profiles from EYO = −20 to −10 years, with a hypermetabolism before hypometabolism in <em>PSEN1</em> mutation carriers. Early increases in plasma GFAP were primarily related to subcortical FDG decreases and cognitive changes in <em>APP</em> mutation carriers compared to non-carriers. We provide evidence for gene-dependent biomarker trajectories in ADAD.<br></p>