Using Photobiomodulation to Alleviate Brain Hypoperfusion in Alzheimer's Disease

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Project Summary Alzheimer's disease is one of the most common and progressive genetic neurodegenerative disorders in the US with more than 5 million people currently living with Alzheimer's disease. A critical gap in knowledge is how vascular brain perfusion dynamics are involved in vascular dementia. This emerging and difficult area of inquiry has limited investigations into the neurovascular system, brain emergent networks, with only indirect applications related to neurological diseases, where the functional role of protein arginine methyltransferases as they relate to brain metabolism, circulation, functional learning and memory are understudied. Here, we seek to investigate protein arginine methyltransferase 4 as an important age and sex-related brain regulatory element to delay vascular cognitive impairment disorders. We recently discovered protein arginine methyltransferase 4 was enhanced in the AD brain in mice and humans. Our central hypothesis is the inhibition of protein arginine methyltransferase 4 via photobiomodulation, a non-invasive therapeutic (808 nm, 35 mW/cm2), can enhance neurovascular coupling, maintain blood-brain-barrier integrity, and attenuate learning/memory deficits in aged 3xTg-AD mice. Therefore, inhibition of PRMT4 in the AD brain can revive microvessel perfusion and hypoperfusion-mediated AD. This is a multi-PI proposal garnering the strengths of Dr. Kevin Lin, a protein arginine methyltransferase expert in cerebral vascular brain perfusion (via two-photon laser scanning microscopy) in various disease states such as AD and stroke/ischemia, and Dr. Quanguang Zhang, an expert in functional behavior outcomes related to AD/ADRD with strengths in photobiomodulation as a clinically relevant therapy.