Physical Exercise Effects on Cognitive Function in Alzheimer's Models

Physical exercise has emerged as a potent non-pharmacological intervention to ameliorate cognitive deficits in experimental models of Alzheimer’s disease. Studies across transgenic mice and toxin-induced paradigms consistently demonstrate that both aerobic and resistance training preserve hippocampal-dependent learning and memory. Mechanistically, exercise enhances synaptic plasticity and neurogenesis, modulates bioenergetic pathways in neurons, and shifts microglial activation toward a neuroprotective phenotype. These adaptations collectively reduce the accumulation of amyloid-β and hyperphosphorylated tau, dampen chronic neuroinflammation and oxidative stress, and promote clearance of toxic protein aggregates. The beneficial effects span early-stage prevention to attenuation of established pathology, underscoring global relevance for ageing populations. Practical applications include structured treadmill regimens and resistance protocols tailored to maintain cognitive resilience, with implications for public health strategies aimed at delaying onset or progression of Alzheimer’s-like impairments.

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Physical Exercise Effects on Cognitive Function in Alzheimer's Models publication trend

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Technical terms

Amyloid-β (Aβ): Peptides that aggregate extracellularly to form plaques implicated in neuronal toxicity.

Microglia: Resident immune cells of the brain that can adopt pro-inflammatory or neuroprotective states.

Neuroplasticity: The capacity of neural circuits to reorganise structurally and functionally in response to experience.

Neurogenesis: Generation of new neurons from progenitor cells, notably within the hippocampal dentate gyrus.

Tau pathology: Abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau in neurons.

References

1. Brain metabolism in Alzheimer’s disease: biological mechanisms of exercise. Translational Neurodegeneration (2023).
2. Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease. Journal of Neuroinflammation (2023).
3. Physical Exercise Inhibits Inflammation and Microglial Activation. Cells (2019).
4. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid. Journal of Neuroinflammation (2008).
5. Treadmill Exercise Decreases Aβ Deposition and Counteracts Cognitive Decline in APP/PS1 Mice, Possibly via Hippocampal Microglia Modifications. Frontiers in Aging Neuroscience (2019).
6. Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice. Journal of Neuroinflammation (2020).
7. Long-term treadmill exercise attenuates tau pathology in P301S tau transgenic mice. Molecular Neurodegeneration (2014).