APOE ‐stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease
Year: 2026
Type: article
Abstract: Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease (AD). However, it is known that other pathways independent of APOE also play a role in AD. Disentangling APOE-dependent and independent effects is instrumental for understanding the biology of AD. We conducted an APOE-stratified multi-omic analysis in multiple large datasets to identify AD-associated plasma proteins and metabolites. More than 64% of the identified proteins were not found in non-APOE stratified studies, and 17% of the proteins showed APOE-specific trends. Mitochondrial dysfunction was associated in AD independently of APOE and was accompanied by disruptions in glucose and lipid metabolism and cell death and increased in inflammatory signaling activation. Lipid upregulation was found in AD cases when compared with controls with the same APOE genotype, indicating that additional factors beyond APOE affect lipid regulation and AD risk. These findings may be informative in guiding the development of effective medications for AD.
Source: Advanced Science
Authors: Fuhai Li, Yike Chen, Daniel Western, Muhammad Ali, Menghan Liu, Katherine Gong, Ying Xu, Joseph Lowery, David M. Holtzman, Chloe Robins, John D. Eicher, Yen‐Ning Huang, ShiWei Liu, Tamina Park, Andrew J. Saykin, Kwangsik Nho, Mahdi Moqri, Richard C. Mohs, Amelia Farinas, Patricia Moran‐Losada, Hamilton Se‐Hwee Oh, Tony Wyss‐Coray, Carlos Cruchaga
Institutions: Washington University in St. Louis, Hope Center for Neurological Disorders, Indiana University Indianapolis, Indiana University School of Medicine, Brigham and Women's Hospital, Harvard University, Global Alzheimer's Platform Foundation, Stanford University, Icahn School of Medicine at Mount Sinai, Stanford Medicine
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,730
Awards: G1007389970, Detailed Proteomic Landscape of Alzheimer Disease, AI models of multi-omic data integration for ming longevity core signaling pathways, G2830398374, G3159755494, USING QUANTITATIVE TRAITS TO IDENTIFY NOVEL GENES FOR ALZHEIMERS DISEASE AND OTHER COMPLEX TRAITS, Pathway discovery, validation and compound identification for Alzheimer's disease, G4505337483, G4970245363, G5005653641, IDENTIFYING RARE VARIANTS THAT INCREASE RISK FOR ALZHEIMER'S DISEASE, G6720674715, G9000005642, G9000015626, G9000016719, G9000044249, G9000045301, G9000060617, G9000060740, G9000068110, G9000090187, G9000096510, G9000097174, G9000099765, G9000121766, G9000128617, G9000128926, G9000158875, G9000218302, G9000226439, G9000237998, G9000244657, G9000266834, G9000314426, Alzheimer's Disease Research Center, AI models of multi-omic data integration for ming longevity core signaling pathways, Alzheimer's MultiOme Data Repurposing: Artificial Intelligence, Network Medicine, and Therapeutics Discovery
OpenAlex ID: W7128064959