@article{fda21fc865a94dbe8cd683f6012585e8,
title = "Network dysfunction in cognitively normal APOE ε4 carriers is related to subclinical tau",
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.",
keywords = "apolipoprotein E, functional connectivity, preclinical Alzheimer's disease, resting state, tau",
author = "Butt, {Omar H.} and Meeker, {Karin L.} and Wisch, {Julie K.} and Schindler, {Suzanne E.} and Fagan, {Anne M.} and Benzinger, {Tammie L.S.} and Carlos Cruchaga and Holtzman, {David M.} and Morris, {John C.} and Ances, {Beau M.}",
note = "Funding Information: Data from the Knight ADRC cohort was funded by NIA grants P50 AG05681 (JCM, PI), P01 AG03991 (JCM, PI), and P01 AG026276 (JCM, PI). We thank all participants at the Knight Alzheimer Disease Research Center for their role in the sample provision and data collection. This work was also supported by the generous support of Barnes-Jewish Hospital, the Knight Alzheimer Disease Research Center, the Hope Center for Neurological Disorders, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, and the Fred Simmons and Olga Mohan Fund. Funding Information: Data from the Knight ADRC cohort was funded by NIA grants P50 AG05681 (JCM, PI), P01 AG03991 (JCM, PI), and P01 AG026276 (JCM, PI). We thank all participants at the Knight Alzheimer Disease Research Center for their role in the sample provision and data collection. This work was also supported by the generous support of Barnes‐Jewish Hospital, the Knight Alzheimer Disease Research Center, the Hope Center for Neurological Disorders, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, and the Fred Simmons and Olga Mohan Fund. Publisher Copyright: {\textcopyright} 2021 the Alzheimer's Association",
year = "2022",
month = jan,
doi = "10.1002/alz.12375",
language = "English",
volume = "18",
pages = "116--126",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
number = "1",
}