Document Type

Journal Article

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School of Medical and Health Sciences




Open Access funding enabled and organized by CAUL and its Member Institutions / National Health and Medical Research Council

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NHMRC Number : GNT1097105

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Sewell, K. R., Rainey-Smith, S. R., Pedrini, S., Peiffer, J. J., Sohrabi, H. R., Taddei, K., . . . Brown, B. M. (2024). The impact of exercise on blood-based biomarkers of Alzheimer’s disease in cognitively unimpaired older adults. GeroScience. Advance online publication.


Physical activity is a promising preventative strategy for Alzheimer’s disease: it is associated with lower dementia risk, better cognition, greater brain volume and lower brain beta-amyloid. Blood-based biomarkers have emerged as a low-cost, non-invasive strategy for detecting preclinical Alzheimer’s disease, however, there is limited literature examining the effect of exercise (a structured form of physical activity) on blood-based biomarkers. The current study investigated the influence of a 6-month exercise intervention on levels of plasma beta-amyloid (A 42, A 40, A 42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) chain in cognitively unimpaired older adults, and as a secondary aim, whether blood-based biomarkers related to cognition. Ninety-nine community-dwelling older adults (69.1 ± 5.2) were allocated to an inactive control, or to moderate or high intensity exercise groups where they cycled twice weekly for six months. At baseline and six months (post-intervention), fasted blood was collected and analysed using single molecule array (SIMOA) assays, and cognition was assessed. Results demonstrated no change in levels of any plasma biomarker from pre- to post-intervention. At baseline, higher NfL was associated with poorer cognition ( = -0.33, SE = 0.13, adjusted p =.042). Exploratory analyses indicated higher cardiorespiratory fitness was associated with higher NfL and GFAP levels in apolipoprotein E (APOE) 4 non-carriers compared to 4 carriers (NfL, = -0.43, SE = 0.19, p =.029; GFAP, = -0.41, SE = 0.20, p =.044), though this association was mediated by body mass index (BMI). These results highlight the importance of considering BMI in analysis of blood-based biomarkers, especially when investigating differences between APOE ε4 carriers and non-carriers. Our results also indicate that longer follow-up periods may be required to observe exercise-induced change in blood-based biomarkers.



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This work is licensed under a Creative Commons Attribution 4.0 License.

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