Changes of the Primary Cilia in Alzheimer's Disease Pathogenesis

Alzheimer's disease (AD), a neurodegenerative disorder intricately linked with aging, poses an escalating global health challenge. Currently, no effective treatment exists for AD. Although the pathological characteristics of AD predominantly emerge in older age, numerous structural and functional alterations in the nervous system may commence early in life or even during developmental stages. Primary cilia, organelles associated with age-related diseases, have not been extensively studied in the context of AD progression. This study initiated an examination of the common pathological features of AD and identified that amyloid-beta (Aβ) plaque deposition resulted in the shortening of primary cilia. In the hippocampus of familial AD mice, there was a significant upregulation of somatostatin receptor 3 (SSTR3) expression. To further elucidate the role of SSTR3 in AD pathology, we knocked out SSTR3 expression in 5 × FAD mice, which resulted in an exacerbation of AD-related pathological features. Our study offers novel insights into the pathological alterations associated with AD.