Network dysfunction in cognitively normal APOE ε4 carriers is related to subclinical tau.

Abstract

Apolipoprotein E (APOE) ε4 allele status is associated with amyloid and tau-related pathological changes related to Alzheimer's disease (AD). However, it is unknown whether brain network changes are related to amyloid beta (Aβ) and/or tau-related pathology in cognitively normal APOE ε4 carriers with subthreshold Aβ accumulation. Resting state functional connectivity measures of network integrity were evaluated in cognitively normal individuals (n=121, mean age 76.6 ± 7.8 years, 15% APOE ε4 carriers, 65% female) with minimal Aβ per cerebrospinal fluid (CSF) or amyloid positron emission tomography. APOE ε4 carriers had increased lateralized connections relative to callosal connections within the default-mode, memory, and salience networks (P=.02), with significant weighting on linear regression toward CSF total tau (P=.03) and CSF phosphorylated tau at codon 181 (P=.03), but not CSF Aβ42 . Cognitively normal APOE ε4 carriers with subthreshold amyloid accumulation may have network reorganization associated with tau.