Exercise and Alzheimer’s disease in individuals with Down syndrome

Abstract

2024Individuals with Down syndrome (DS) face a heightened risk of developing Alzheimer's disease (AD) due to triplication of chromosome 21, which harbors the amyloid precursor protein (APP) gene. The resultant overexpression of APP leads to elevated amyloid plaque production, a hallmark of AD neuropathology. With increasing longevity, age-related dementia of the AD type is prevalent in people with DS. Given the need for targeted interventions, we explore exercise as a potential avenue to mitigate AD onset in this vulnerable population. While exercise is known to modulate AD pathways in the general population, its specific effects on individuals with DS remain understudied. We review three AD pathophysiological pathways—oxidative stress, mitochondrial dysfunction, and neuroinflammation—and highlight evidence demonstrating exercise's potential to modify these pathways. Clinical trials in the general population demonstrate exercise's efficacy in reducing neuroinflammation and oxidative stress, suggesting its promise as a non-pharmacological intervention for AD. Longitudinal exercise studies in DS are lacking, warranting further investigation into exercise-induced biomarkers and neuroprotective mechanisms. To advance this field, blood-based biomarker exploration and longitudinal studies are needed in further exercise trials in individuals with DS. This review serves to establish a framework to deepen the knowledge where comprehensive data exists, such as oxidative stress studies. The framework also extends to where there is a paucity of data, including mitochondrial dysfunction and neuroinflammation. Future research should focus on elucidating exercise-induced biomarkers, optimizing exercise prescriptions, and exploring novel pathways, ultimately paving the way for effective AD prevention and management strategies in this vulnerable population and beyond