The Association Between Alzheimer's Disease-Related Markers and Physical Activity in Cognitively Normal Older Adults

Abstract

Previous studies have indicated that physical activity may be beneficial in reducing the risk for Alzheimer's disease (AD), although the underlying mechanisms are not fully understood. The goal of this study was to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers (i.e., measured using a novel high-performance mass spectrometry-based assay), in apolipoprotein E (APOE) ε4 carriers and noncarriers. We evaluated 143 cognitively normal older adults, all of whom had brain amyloid deposition assessed using positron emission tomography and had their physical activity levels measured using the International Physical Activity Questionnaire (IPAQ). We observed an inverse correlation between brain amyloidosis and plasma beta-amyloid (Aβ)_1-42 but found no association between brain amyloid and plasma Aβ_1-40 and amyloid precursor protein (APP)_669-711. Additionally, higher levels of physical activity were associated with lower plasma Aβ_1-40, Aβ_1-42, and APP_669-711 levels in APOE ε4 noncarriers. The ratios of Aβ_1-40/Aβ_1-42 and APP_669-711/Aβ_1-42, which have been associated with higher brain amyloidosis in previous studies, differed between APOE ε4 carriers and non-carriers. Taken together, these data indicate a complex relationship between physical activity and brain amyloid deposition and potential blood-based AD biomarkers in cognitively normal older adults. In addition, the role of APOE ε4 is still unclear, and more studies are necessary to bring further clarification.

Keywords: APOE genotype; Alzheimer's disease; amyloid; biomarkers; physical activity.

Figure 1

Schematic representation of how physical activity (PA) may reduce Aβ generation with consequently reduced transport of Aβ₁₋₄₂ across the blood-brain barrier (BBB) into circulation. In apolipoprotein E (APOE) ε4– (A), increased intensity of PA is followed by a reduced generation of Aβ₁₋₄₂ with consequently reduced plaque formation in the brain and reduced transport of Aβ₁₋₄₂ in the bloodstream. In APOE ε4+ (B), the lower levels of Aβ₁₋₄₂ in the bloodstream are a consequence of increased Aβ₁₋₄₂ retention in the brain with greater plaque formation. The intensity of PA does not appear to affect Aβ₁₋₄₂ plasma levels.