Physical activity mitigates dysfunction of the neuro-vascular unit in a mouse model of Alzheimer’s disease

The Neurovascular Unit (NVU) dynamically regulates oxygen supply to satisfy neural metabolic demand. Amyloid-β (Aβ) accumulation and hyperphosphorylated Tau in Alzheimer's disease (AD) disrupt the NVU. Empirical evidence strongly indicates that physical activity (PA) reduces the rate of cognitive impairment, but the physiological mechanism(s) PA's neuroprotective benefits remain unclear. We propose PA improves the brain parenchymal oxygenation and reduces metabolic deficits. Using the novel oxygen sensitizer, Oxyphor 2P, and 2-photon phosphorescence lifetime imaging (2P-PLIM), our results indicate that the PA shows the potential to curtail AD progression by increasing microvascular oxygenation and preserving NVU function.