- October 14, 2025
- Carlos Cruchaga, et al., Washington University School of Medicine, St. Louis
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Alzheimer's Disease
Sample Type:
Plasma
Abstract
Age and APOE ε4 are major risk factors for Alzheimer’s disease (AD), while sex differences exist in disease prevalence and progression. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and AD. To examine proteomic changes due to age, sex and apolipoprotein E (APOE) ε4 along with amyloid status before clinical AD occurs, we profiled 6,175 proteins in the CSF from 994 cognitively normal individuals aged 43–91 years. We identified and replicated 2,172 age-associated, 711 sex-associated, 193 APOE ε4-associated and 1,807 amyloid-associated proteins, with extensive overlap suggesting their interplay. These CSF-specific signatures were distinct from those in plasma. Network analysis revealed two proteomic modules—M2 (age-associated, sex-associated and amyloid-associated) and M6 (age-associated and sex-associated)—which were linked to neuropsychiatric and aging-related diseases. Together, our study provides proteomic changes during the early phase of AD, which may help identify new therapeutic targets of AD.
Authors & Affiliations
Dahun Seo¹², Anh N. Do¹³⁴, Gyujin Heo¹⁴, Jiseon Kwon¹⁴, Soomin Song¹⁴, Catherine Apio¹⁵, Cheolmin Matthew Lee¹⁶, Jigyasha Timsina¹⁴, Katherine Gong¹⁴, Yike Chen¹⁴, Menghan Liu¹⁴, Pat Kohlfeld¹⁴, John Budde¹⁴, Merce Boada⁷⁸, Adelina Orellana⁷, Maria Victoria Fernandez⁷, Agustin Ruiz⁷⁸⁹, John C. Morris¹⁰¹¹, Suzanne E. Schindler¹⁰¹¹, Laura Ibanez¹¹¹², Taesung Park²⁵, Carlos Cruchaga¹⁴¹⁰¹², and Yun Ju Sung¹³⁴
¹ NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA
² Department of Statistics, Seoul National University, Seoul, Korea
³ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
⁴ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
⁵ Interdisciplinary Programs in Bioinformatics, Seoul National University, Seoul, Korea
⁶ Health Sciences Integrated Program, Northwestern University, Chicago, IL, USA
⁷ Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain
⁸ Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, Madrid, Spain
⁹ Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, TX, USA
¹⁰ The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
¹¹ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
¹² Hope Center, Washington University School of Medicine, St. Louis, MO, USA
