Omar H Butt1, Karin L Meeker1, Julie K Wisch1, Suzanne E Schindler1, Anne M Fagan1,2,3, Tammie L S Benzinger4, Carlos Cruchaga2,3,5, David M Holtzman1,2,3, John C Morris1,2,3, Beau M Ances1,2,3,4. 1. Department of Neurology, Washington University in Saint Louis, Saint Louis, Missouri, USA. 2. Knight Alzheimer Disease Research Center, Washington University in Saint Louis, St. Louis, Missouri, USA. 3. Hope Center for Neurological Disorders, Washington University in Saint Louis, St. Louis, Missouri, USA. 4. Department of Radiology, Washington University in Saint Louis, Saint Louis, Missouri, USA. 5. Department of Psychiatry, Washington University in Saint Louis, Saint Louis, Missouri, USA.
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.
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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