Saman Hemani

Introduction: Alzheimer’s Disease (AD) is a neurodegenerative disorder of aging that affects over 24 million people globally presenting primarily as a progressive loss of memory, language impairment, executive function, as well as hallucinations^1-5. Sporadic AD typically presenting in older adults (70+)and occurs in 95% of AD cases, whereas Familial AD presents in younger patients, occurs in 1-5% of AD cases, and has been linked to mutations in the PS1/PS2 gene. The dual pathology of intracellular hyperphosphorylated tau protein aggregates and extracellular amyloid-β plaque buildup due to increased β-secretase activity are characteristic of AD^1,4. The role of the immune system is also implicated. The paradoxical role of microglia in AD pathogenesis is due to reduced microglial activity in early AD³ leading to increased amyloid aggregation, followed by an overactivation of the immune response which leads to potential microglial destruction of neuronal bodies⁷. This review evaluates Gamma ENtrainment Using Sensory stimuli (GENUS) technology via auditory stimulation and combined visual/auditory stimulation on neuronal activity and effects on learning in AD. Methods: Auditory tone and visual flicker stimulation in a 40 Hz gamma frequency was used to study the effects on amyloid buildup and cognitive function in 5XFAD mice models. The. GENUS treatment (7 days) glial reactivity, amyloid load, and recognition and spatial memory were measured⁵. Results:  5XFAD mice exposed to 40 Hz gamma stimulation showed a significant reduction of Aβ peptide levels in hippocampus CA1 as compared to the control group, with up-regulation of  genes primarily in microglia, leading to transformation in microglial activation and Aβ uptake⁶. GENUS treatment decreased amyloid load in the AC, CA1, visual cortex, and uniquely, the primary frontal cortex. Auditory GENUS observed an increase in Aβ uptake by microglia and vascular dilation leading to Aβ clearance, which correlated with improved spatial and recognition memory tasks in AD mice models⁵. Conclusion: Studies have shown that microglial activation can have a paradoxical effect on the pathology of AD, however, early detection of AD symptoms and use of GENUS therapy can reduce Aβ and tau pathology without neuronal loss, delaying the progression and reducing the symptomatology of AD.

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