The association of Alzheimer's disease and related dementias blood-based biomarkers with depressive symptoms.

INTRODUCTION: Depressive symptoms are common in older adults and have been associated with the risk of Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD), but the mechanisms and biomarkers underlying this association remain unclear. METHODS: We included baseline data from 11,947 non-demented adults aged ≥ 70 years at enrollment in the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial. Linear regressions were used to examine cross-sectional associations between AD/ADRD blood-based biomarkers (BBMs) and baseline depressive symptoms. Interactions between sex or apolipoprotein E (APOE) ε4 carrier status and BBMs were examined. RESULTS: Higher glial fibrillary acidic protein (GFAP) was associated with higher depressive symptoms. We did not observe an association between amyloid beta 42/40 ratio, phosphorylated tau181, or neurofilament light chain with depressive symptoms; interactions between sex or APOE ε4 with depressive symptoms were not significant. DISCUSSION: In this large, community-based cohort of older adults, plasma GFAP was associated with greater depressive symptoms. HIGHLIGHTS: Plasma glial fibrillary acidic protein was associated with depressive symptoms. Neuroinflammation may underlie depressive symptoms in this group. Future research is needed to examine sex differences in this association.