Targeting MicroRNA-485-3p Blocks Alzheimer's Disease Progression

Alzheimer's disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction. With only one FDA-approved therapy, effective treatment strategies for AD are urgently needed. In this study, we found that microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues, cerebrospinal fluid, and plasma of patients with AD, and its antisense oligonucleotide (ASO) reduced A beta plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. Mechanistically, miR-485-3p ASO enhanced A beta clearance via CD36-mediated phagocytosis of A beta in vitro and in vivo. Furthermore, miR-485-3p ASO administration reduced apoptosis, thereby effectively decreasing truncated tau levels. Moreover, miR-485-3p ASO treatment reduced secretion of proinflammatory cytokines, including IL-1 beta and TNF-alpha, and eventually relieved cognitive impairment. Collectively, our findings suggest that miR-485-3p is a useful biomarker of the inflammatory pathophysiology of AD and that miR-485-3p ASO represents a potential therapeutic candidate for managing AD pathology and cognitive decline.

Automated summary

Treatment with miR-485-3p ASO reduces A beta plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in an AD transgenic mouse model by enhancing A beta clearance and reducing apoptosis. Additionally, miR-485-3p ASO administration decreases proinflammatory cytokine secretion, ultimately alleviating cognitive impairment.