Treadmill Exercise Decreases Aβ Deposition and Counteracts Cognitive Decline in APP/PS1 Mice, Possibly via...

Area of Science:

• Neuroscience
• Exercise Physiology
• Molecular Biology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
• Microglia-mediated neuroinflammation and oxidative stress are implicated in AD pathogenesis.
• The precise mechanisms by which exercise impacts AD progression remain unclear.

Purpose of the Study:

• To investigate the effects of treadmill exercise on amyloid-β (Aβ) deposition, cognitive function, and neuroinflammation in a mouse model of early Alzheimer's disease.
• To analyze the role of microglia polarization and oxidative stress in mediating the benefits of exercise.

Main Methods:

• Amyloid precursor protein (APP)/PS1 mice were subjected to 12 weeks of treadmill exercise.
• Cognitive function was assessed using hippocampal-dependent memory tests.
• Hippocampal tissues were analyzed for Aβ deposition, pro- and anti-inflammatory factors, microglia phenotype (M1/M2), and oxidative stress markers (MDA, SOD, Mn-SOD).

Main Results:

• Treadmill exercise preserved hippocampal cognitive function in APP/PS1 mice.
• Exercise significantly suppressed Aβ accumulation in the hippocampus.
• Neuroinflammation was inhibited, evidenced by reduced pro-inflammatory factors and increased anti-inflammatory mediators, linked to a shift from M1 to M2 microglia phenotype.
• Oxidative stress was attenuated, with decreased MDA levels and increased SOD and Mn-SOD activities.

Conclusions:

• Treadmill exercise demonstrates potential therapeutic benefits for early-stage Alzheimer's disease.
• Exercise may prevent cognitive decline and reduce Aβ pathology by modulating microglia-mediated neuroinflammation and oxidative stress.
• These findings highlight exercise as a viable non-pharmacological intervention for Alzheimer's disease.