RAB10: an Alzheimer’s disease resilience locus and potential drug target

Abstract

Alzheimer’s disease (AD) is mainly a late-onset neurodegenerative disorder. Substantial efforts have been made to solve the complex genetic architecture of AD as a means to identify therapeutic targets. Unfortunately, to date, no disease-altering therapeutics have been developed. As therapeutics are likely to be most effective in the early stages of disease (ie, before the onset of symptoms), a recent focus of AD research has been the identification of protective factors that prevent disease. One example is the discovery of a rare variant in the 3′-UTR of RAB10 that is protective for AD. Here, we review the possible genetic, molecular, and functional role of RAB10 in AD and potential therapeutic approaches to target RAB10.

Keywords:

• Alzheimer’s disease
• RAB10
• retromer
• APP
• resilience
• GTPase

Acknowledgments

This work was supported by grants from the National Institutes of Health (K01 AG046374, U01 AG052411, R01 AG062359, and RF1 AG054052).

Disclosure

The authors report no conflicts of interest in this work.