1H-MRSI of white matter in cognitively unimpaired elderly for the detection of early Alzheimer’s disease pathological changes

Motivation: APOE4 has been linked to increased amyloid and tau deposition and microstructural WM changes in Alzheimer’s, but despite the major role of APOE in myelination, whether WM metabolism is altered in individuals at risk for Alzheimer’s remains unknown. Goal(s): To examine if choline, a constituent of myelin and a marker of membrane turnover, is associated with APOE4, CSF p-tau181 (a marker of tau burden), and WM volume (a marker of neurodegeneration). Approach: Cognitively unimpaired elderly with and without APOE4 underwent 1H-MRSI. Relationships between WM choline, APOE4, tau, and WM volume were assessed. Results: No associations were found between WM choline and any marker. Impact: WM metabolism is not associated with genotype, tau, or neurodegeneration in healthy elderly, but given that amyloid deposition is the earliest Alzheimer’s pathological hallmark, additional investigations with amyloid biomarkers are needed to better characterize WM metabolism in the preclinical stage.