Network dysfunction in cognitively normal APOE ε4 carriers is related to subclinical tau. Issue 1 (18th May 2021)

• Record Type: Journal Article
• Authors: Butt, Omar H.; Meeker, Karin L.; Wisch, Julie K.; Schindler, Suzanne E.; Fagan, Anne M.; Benzinger, Tammie L.S.; Cruchaga, Carlos; Holtzman, David M.; Morris, John C.; Ances, Beau M.
• Is Part Of: Alzheimer's & dementia. Volume 18:Issue 1(2022)
• Page Start: 116
• Page End: 126
• Publication Date: 2021-05-18
• Subjects: apolipoprotein E -- functional connectivity -- preclinical Alzheimer's disease -- resting state -- tau; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.12375
• Languages: English
• ISSNs: 1552-5260

Abstract

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.