O2-05-05: CORRELATION OF CSF PHOSPHOLIPIDS AND ALZHEIMER'S DISEASE NEUROPATHOLOGY IN THE MAYO CLINIC STUDY OF AGING

Lipids play important roles in many brain functions, but their roles in the development and progression of Alzheimer's disease (AD) dementia and pathology are not completely defined. CSF phosphorylated tau (pTau) and neurofilament light (NFL) are valid proxies for neuropathological changes of AD in the brain. The objective of this study is to examine the cross-sectional associations between CSF phospholipids and proxies of AD associated neuropathology or cognition in cognitively unimpaired older adults. This study included cognitively unimpaired participants (N=739) enrolled in the Mayo Clinic Study of Aging, aged 50-95, with data available for 8 CSF phospholipids (PC aa [14:0, 14:0], PC aa [16:0, 16:0], PC aa [16:0, 18:2], PC aa [16:0, 22:6], PC aa [18:0, 18:0], PC aa [18:0, 18:1], PC aa [18:0, 20:4], PC aa [18:1, 18:1]), CSF pTau, NFL, and cognition. These 8 PCs were measured using analyte specific standards to provide chain length and position specific information on fatty acyl groups. For example, PC aa (16:0, 18:2) means fatty acyl 16:0 and 18:2 at sn-1 and sn-2 position, respectively. Univariable and multivariable linear regression models were used to examine the cross-sectional associations between CSF phospholipids (models in Z scores) and CSF neuropathological biomarkers or cognitive measures (Global, Language, Memory, Attention, Visuospatial Function). Multivariable models were adjusted for age, gender and APOE genotype. Elevated brain amyloid deposition, sex, and the presence of APOE4 allele were also examined as effect modifiers. Bonferroni adjusted p-value of less than 0.00625 was used to indicate statistical significance. All 8 CSF phospholipids except PC aa [18:0, 18:0] were significantly associated with CSF NFL concentrations after multivariate adjustment for age, sex, and presence of APOE4 allele. CSF phospholipids were not associated with CSF pTau or cognition. The interactions of all 8 CSF phospholipids with male gender were also significantly associated with CSF NFL concentrations. Because CSF NFL is a non-specific marker of neurodegeneration, strong associations between CSF phospholipids and CSF NFL suggest that phospholipids levels in CSF may indicate neurodegeneration in the brain.