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APOE GENOTYPE, AGE AND SEX AFFECT LONGITUDINAL CHANGE OF CEREBROSPINAL FLUID BIOMARKERS: FINDINGS FROM THE SWEDISH BIOFINDER COHORT
Abstract
Aims
Aims
In this study we assessed the effects of APOE genotype, age, and sex on the longitudinal change of CSF biomarkers of Alzheimer’s disease (p-tau181), astrocytosis (YKL-40, GFAP) and microglial activation (sTREM2) in the longitudinal Swedish BioFINDER cohort.
Methods
Methods
CSF was collected at baseline and 2-, 4-, 6-, 8- and 10-years’ follow-up from cognitively unimpaired (CU, n=801) or MCI (n=265) patients. Aβ status was defined based on the CSF Aβ42/40 ratio in CSF. Biomarkers were measured with NeuroToolKit (Roche). Reliability of change index (RCI) was calculated in Ab negative CU to define “stable” (slope of change over time=+/-RCI) and “increasers” (slope>RCI) groups in the cohort. Logistic regression was used to assess effects of APOE, age and sex on the “stable” vs. “increaser” outcome.
Results
Results
Increases in CSF p-tau181 over time due to APOE genotype are fully mediated by Aβ+ status (p<0.0001, OR 7.6). GFAP and sTREM2 increased less in women than in men over time, independently of Aβ status (GFAP: p=0.01, OR 0.6; sTREM2: p=0.003, OR 0.4). Increase in YKL-40 over time was affected by age, independently of Aβ status (p=0.02, OR 1.1).
Conclusions
Conclusions
Aβ status, age, and sex affect longitudinal change of CSF biomarkers. The present findings warrant for adjustment for these variables in longitudinal studies.