Work

CSF and plasma lipid profiling predicts risk of cognitive impairment in cognitively unimpaired older adults

Year: 2026

Type: article

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.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.71924