Public Health

Area of Science:

• Neuroscience
• Gerontology
• Public Health

Background:

• Dementia is increasingly preventable through lifestyle changes, with 14 modifiable risk factors identified.
• Physical activity is a key mid-life risk factor for dementia, linked to brain biomarkers but less so to blood-based markers.
• The relationship between physical activity and blood-based Alzheimer's disease (AD) biomarkers requires further investigation.

Purpose of the Study:

• To investigate the association between physical activity and blood-based AD biomarkers.
• To determine if the apolipoprotein E epsilon 4 (APOE-ε4) gene influences the relationship between physical activity and AD biomarkers.

Main Methods:

• 739 healthy participants from the ISLAND study completed physical activity questionnaires and provided blood samples.
• Blood biomarkers analyzed included serum neurofilament light (NfL), serum glial fibrillary acidic protein (GFAP), and plasma phosphorylated tau 181 (p-tau 181).
• Generalized linear regression models assessed the association between physical activity (MET score) and AD biomarkers, considering APOE-ε4 status.

Main Results:

• Greater physical activity was significantly associated with lower serum GFAP levels.
• This association was moderated by APOE-ε4 status; it was significant in APOE-ε4 negatives but not in APOE-ε4 positives.
• Vigorous physical activity showed the strongest association with serum GFAP, while light and moderate activity did not.
• No significant relationship was found between physical activity and p-tau 181 or NfL.

Conclusions:

• Physical activity is associated with serum GFAP, a blood-based biomarker for AD.
• The APOE-ε4 genotype modifies the association between physical activity and GFAP.
• Physical activity represents a promising target for community interventions aimed at reducing dementia risk and its early biological markers.