Raghavendra Rao
Independent Researcher
Greater Noida, India
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, synaptic dysfunction, and accumulation of amyloid-beta plaques. The presence of the APOE4 allele significantly increases the risk of developing late-onset AD compared to other APOE isoforms. While traditional therapeutic strategies have shown limited efficacy in targeting this genetic risk factor, recent advancements in CRISPR-Cas9 gene editing offer a transformative approach. This study explores a preclinical therapeutic framework using CRISPR to selectively suppress APOE4 expression in mouse models genetically engineered to express the human variant. The research examines CRISPR guide RNA (gRNA) design, vector delivery systems, and the molecular, behavioral, and histopathological outcomes of APOE4 silencing. Results suggest a notable reduction in amyloid plaque deposition, improved cognitive performance in behavioral assays, and enhanced synaptic integrity. This novel intervention demonstrates the promise of genome editing for precise modulation of high-risk alleles and may lay the groundwork for future human therapeutic applications. The framework presented is an essential step toward personalized genetic therapies for Alzheimer’s disease.
Keywords
CRISPR-Cas9, APOE4, Alzheimer’s disease, gene editing, mouse models, neurodegeneration, therapeutic framework, genome engineering, amyloid plaques, personalized medicine
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