CSF and plasma lipid profiling predicts risk of cognitive impairment in cognitively unimpaired older adults
10 affiliations
- 1Department of Neuroscience Mayo Clinic Jacksonville Florida USA
- 2Department of Quantitative Health Sciences Mayo Clinic Jacksonville Florida USA
- 3Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio San Antonio Texas USA
- 4Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center Washington University School of Medicine St. Louis Missouri USA
- 5Division of Biostatistics Washington University School of Medicine St. Louis Missouri USA
- 6Department of Quantitative Health Sciences Mayo Clinic Rochester Minnesota USA
- 7Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA
- 8Departments of Structural Biology and Developmental Neurobiology St. Jude Children's Research Hospital Memphis Tennessee USA
- 9Division of Life Science and State Key Laboratory of Nervous System Disorders The Hong Kong University of Science and Technology Clear Water Bay Hong Kong China
- 10Departments of Neurology Mayo Clinic Rochester Minnesota USA
Abstract
INTRODUCTION: Age‐related cognitive decline and Alzheimer's disease (AD) are strongly influenced by lipid metabolism, yet how central and peripheral lipid profiles relate to disease risk before symptom onset remains unclear.
METHODS: We performed comprehensive shotgun lipidomics in cerebrospinal fluid (CSF) and plasma from cognitively unimpaired older adults, with longitudinal follow‐up for Clinical Dementia Rating (CDR) conversion.
RESULTS: CSF lipidomes were primarily associated with age and established CSF AD biomarkers, whereas plasma lipid profiles were strongly influenced by sex. Specific CSF phosphatidylethanolamine subspecies showed robust positive associations with CSF total tau, phosphorylated tau 181, neurogranin, and chitinase‐3 like‐1. CSF triacylglycerol TAG(C49:6), phosphatidylglycerol PG(18:0‐18:1), cholesteryl ester CE(20:3), and phosphatidylethanolamine PE(D16:0‐18:1) independently predicted CDR conversion, improving risk prediction. Plasma sphingomyelin subspecies were modestly associated with cognitive decline risk.
DISCUSSION: These findings identify distinct CSF and plasma lipid signatures linked to preclinical cognitive decline and highlight brain lipid metabolism as a promising source of predictive biomarkers and therapeutic targets.
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BibTeX
@article{kanekiyo2026plasma,
title = {{CSF and plasma lipid profiling predicts risk of cognitive impairment in cognitively unimpaired older adults}},
author = {Takahisa Kanekiyo and Launia J. White and Hongping Ye and Yingxue Ren and Jason D. Ulrich and Ana‐Caroline Raulin and Alla Alnobani and Chengjie Xiong and Yan W. Asmann and Maria Vassilaki and Alicia Algeciras‐Schimnich and Junmin Peng and Fatima S. Amtashar and Suzanne E. Schindler and David M. Holtzman and Guojun Bu and Ronald C. Petersen and Michael G. Heckman and Xianlin Han},
journal = {Alzheimer's \& Dementia},
year = {2026},
month = oct,
doi = {10.1002/alz.71924},
url = {https://doi.org/10.1002/alz.71924},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - CSF and plasma lipid profiling predicts risk of cognitive impairment in cognitively unimpaired older adults
AU - Takahisa Kanekiyo
AU - Launia J. White
AU - Hongping Ye
AU - Yingxue Ren
AU - Jason D. Ulrich
AU - Ana‐Caroline Raulin
AU - Alla Alnobani
AU - Chengjie Xiong
AU - Yan W. Asmann
AU - Maria Vassilaki
AU - Alicia Algeciras‐Schimnich
AU - Junmin Peng
AU - Fatima S. Amtashar
AU - Suzanne E. Schindler
AU - David M. Holtzman
AU - Guojun Bu
AU - Ronald C. Petersen
AU - Michael G. Heckman
AU - Xianlin Han
PY - 2026
DA - 2026/10/27
JO - Alzheimer's & Dementia
DO - 10.1002/alz.71924
UR - https://doi.org/10.1002/alz.71924
AB - INTRODUCTION: Age‐related cognitive decline and Alzheimer's disease (AD) are strongly influenced by lipid metabolism, yet how central and peripheral lipid profiles relate to disease risk before symptom onset remains unclear. METHODS: We performed comprehensive shotgun lipidomics in cerebrospinal fluid (CSF) and plasma from cognitively unimpaired older adults, with longitudinal follow‐up for Clinical Dementia Rating (CDR) conversion. RESULTS: CSF lipidomes were primarily associated with age and established CSF AD biomarkers, whereas plasma lipid profiles were strongly influenced by sex. Specific CSF phosphatidylethanolamine subspecies showed robust positive associations with CSF total tau, phosphorylated tau 181, neurogranin, and chitinase‐3 like‐1. CSF triacylglycerol TAG(C49:6), phosphatidylglycerol PG(18:0‐18:1), cholesteryl ester CE(20:3), and phosphatidylethanolamine PE(D16:0‐18:1) independently predicted CDR conversion, improving risk prediction. Plasma sphingomyelin subspecies were modestly associated with cognitive decline risk. DISCUSSION: These findings identify distinct CSF and plasma lipid signatures linked to preclinical cognitive decline and highlight brain lipid metabolism as a promising source of predictive biomarkers and therapeutic targets.
SN - 1552-5260
SN - 1552-5279
ER -