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Alzheimer's disease (AD) is characterized by the presence of amyloid β (Aβ) plaques, neurofibrillary tangles, and neurodegeneration, evidence of which may be detected in vivo via cerebrospinal fluid (CSF) sampling. Physical activity (PA) has emerged as a possible modifier of these AD‐related pathological changes. Consequently, the aim of this study was to cross‐sectionally examine the relationship between objectively measured PA and CSF levels of Aβ42 and tau in asymptomatic late‐middle‐aged adults at risk for AD.    Methods  Eighty‐five cognitively healthy late‐middle‐aged adults (age = 64.31 years, 61.2% female) from the Wisconsin Registry for Alzheimer's Prevention participated in this study. They wore an accelerometer (ActiGraph GT3X+) for one week to record free‐living PA, yielding measures of sedentariness and various intensities of PA (i.e., light, moderate, and vigorous). They also underwent lumbar puncture to collect CSF, from which Aβ42, total tau, and phosphorylated tau were immunoassayed. Regression analyses were used to examine the association between accelerometer measures and CSF biomarkers, adjusting for age, sex, and other relevant covariates.    Results  Engagement in moderate PA was associated with higher Aβ42 ( P  = .008), lower total tau/Aβ42 ( P  = .006), and lower phosphorylated tau/Aβ42 ( P  = .030). In contrast, neither light nor vigorous PA was associated with any of the biomarkers. Increased sedentariness was associated with reduced Aβ42 ( P  = .014).    Discussions  In this cohort, moderate PA, but not light or vigorous, was associated with a favorable AD biomarker profile, while sedentariness was associated with greater Aβ burden. These findings suggest that a physically active lifestyle may play a protective role against the development of AD.

Moderate intensity physical activity associates with CSF biomarkers in a cohort at risk for Alzheimer's disease