Midlife physical activity was inversely associated with plasma NfL and GFAP at age 67, suggesting that midlife PA may reduce risk for neurodegeneration in older age via amyloid-independent mechanisms.
Physical activity at age 56 was inversely associated with neurofilament light chain (NfL) levels at age 67.
Physical activity at age 56 was inversely associated with glial fibrillary acidic protein (GFAP) levels at age 67.
Physical activity at age 56 was not significantly associated with phosphorylated tau 217 (p-tau217) or the amyloid beta 42/40 ratio at age 67.
Physical activity at age 67 was not reported as significantly associated with any of the AD-related biomarkers at age 67.
The study population consisted entirely of male twins from the Vietnam Era Twin Study of Aging, assessed prospectively across approximately one decade.
This research suggests that being physically active in midlife (around age 56) is linked to lower levels of certain brain damage markers in blood about a decade later (around age 67). Specifically, men who were more physically active at age 56 had lower levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) — two proteins that signal nerve cell damage and brain cell stress — when measured at age 67. However, physical activity was not linked to markers more directly related to amyloid plaques, which are a hallmark of Alzheimer's disease. This distinction is important because it suggests that the brain-protective effects of midlife exercise may work through pathways that are separate from the amyloid buildup traditionally associated with Alzheimer's disease. In other words, staying active in middle age might help protect the brain through mechanisms involving general neurodegeneration and inflammation rather than by preventing amyloid accumulation specifically. Physical activity measured closer to age 67 did not show the same associations, hinting that the timing of exercise — particularly during midlife — may matter. The study followed 564 male twins over roughly a decade, which provides stronger evidence of a time-ordered relationship between exercise and brain health than studies that only measure both at one point in time. However, because the sample was exclusively men who served in the military during the Vietnam era, it is unclear whether these findings would apply equally to women or more diverse populations.
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Upload Your LabsIso-Markku P, Tu X, Rissman R, Gillespie N, Elman J, Fennema-Notestine C, et al.. (2026). Prospective study on physical activity and Alzheimer's disease-related biomarkers.. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71755