Physical activity and blood-based biomarkers of neurodegeneration in community dwelling Australians from ISLAND (Island Study Linking Ageing and Neurodegenerative Disease)

INTRODUCTION: Physical activity, a key modifiable risk factor for dementia, has been associated with biomarkers of neurodegeneration in the central nervous system, but less is known regarding blood-based biomarkers. METHODS: A total of 739 cognitively healthy participants (aged 50-83 years) from ISLAND (Island Study Linking Ageing and Neurodegenerative Disease) completed a battery of online surveys. Self-reported physical activity was assessed based on daily metabolic equivalent, and a blood sample was analyzed for serum neurofilament light chain, serum glial fibrillary acidic protein (GFAP), plasma phosphorylated tau, and genotyped for apolipoprotein E (APOE) ε4. RESULTS: Higher self-reported physical activity was significantly associated with lower log-transformed concentrations of GFAP (pg/mL, β = -0.022, P = 0.009) in fully adjusted generalized linear regression models. Subgroup analysis revealed this association was only significant in APOE ε4 non-carriers. DISCUSSION: This cross-sectional study provides novel evidence for the association of physical activity with blood-based biomarkers of neurodegeneration, and how APOE ε4 presence modifies this relationship. HIGHLIGHTS: We looked at a large-scale (n = 739) community cohort of healthy Australians > 50 years of age.Physical activity (PA) levels were related to blood-based biomarkers of neurodegeneration.Higher PA was associated with lower serum glial fibrillary acidic protein (GFAP).Apolipoprotein E ε4 and PA intensity impacted this association.This novel finding provides a foundation for targeted physical activity interventions.