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

Abstract

INTRODUCTION\nApolipoprotein 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.\n\n\nMETHODS\nResting state functional connectivity measures of network integrity were evaluated in cognitively normal individuals (n\xa0=\xa0121, 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.\n\n\nRESULTS\nAPOE ε4 carriers had increased lateralized connections relative to callosal connections within the default-mode, memory, and salience networks (P\xa0=\xa0.02), with significant weighting on linear regression toward CSF total tau (P\xa0=\xa0.03) and CSF phosphorylated tau at codon 181 (P\xa0=\xa0.03), but not CSF Aβ42 .\n\n\nDISCUSSION\nCognitively normal APOE ε4 carriers with subthreshold amyloid accumulation may have network reorganization associated with tau.