Staging biomarkers in preclinical autosomal dominant Alzheimer's disease by estimated years to symptom onset

Abstract

Introduction: Staging preclinical Alzheimer disease (AD) by the expected years to symptom onset (EYO) in autosomal dominant AD (ADAD) through biomarker correlations is important.

Methods: We estimated the correlation matrix between EYO/cognition and imaging/CSF biomarkers, and searched for the EYO cutoff where a change in the correlations occurred before and after the cutoff among the asymptomatic mutation carriers of ADAD. We then estimated the longitudinal rate of change for biomarkers/cognition within each preclinical stage defined by the EYO.

Results: Based on the change in the correlations, the preclinical ADAD was divided by EYOs -7 and -13 years. Mutation carriers demonstrated a temporal ordering of biomarker/cognition changes across the three preclinical stages.

Discussion: Duration of each preclinical stage can be estimated in ADAD, facilitating better planning of prevention trials with the EYO cutoffs under the recently released FDA guidance. The generalization of these results to sporadic AD warrants further investigation.

Keywords: Autosomal dominant Alzheimer disease; Biomarkers; Dominantly inherited Alzheimer Network; Preclinical Alzheimer disease.