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  • Title: Network dysfunction in cognitively normal APOE ε4 carriers is related to subclinical tau.
    Author: Butt OH, Meeker KL, Wisch JK, Schindler SE, Fagan AM, Benzinger TLS, Cruchaga C, Holtzman DM, Morris JC, Ances BM.
    Journal: Alzheimers Dement; 2022 Jan; 18(1):116-126. PubMed ID: 34002449.
    Abstract:
    INTRODUCTION: 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. METHODS: 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. RESULTS: 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 . DISCUSSION: Cognitively normal APOE ε4 carriers with subthreshold amyloid accumulation may have network reorganization associated with tau.
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