A collaborative research group led by Koichi Ozaki, director of the Clinical Genome Analysis Promotion Department of the National Center for Geriatrics and Gerontology, discovered a gene mutation peculiar to Japanese people that increases the risk of developing Alzheimer's disease.
Sporadic Alzheimer's disease (LOAD) accounts for more than half of dementia and is caused by a complex interaction of numerous environmental and genetic factors.It is known that the contribution of genetic factors to the onset is large, 60% to 80%, but most of the genetic factors of this disease have not yet been clarified.Although TREM2 gene mutations have been reported as a risk of developing white patients, few carriers have been found in Japan, and it has been thought that there are risk gene mutations peculiar to Japanese.
Therefore, in this study, we performed an exome sequence analysis of genomic DNA derived from Japanese patients stored in the biobank of the National Center for Geriatrics and Gerontology for the purpose of searching for LOAD risk genes in Japanese.As a result, a mutation on the SHARPIN gene was identified as a gene mutation involved in the onset of Alzheimer's disease in Japanese.Furthermore, it was revealed that this gene mutation reduces the function of the SHARPIN protein associated with immune function.
This study suggests that mutations in the SHARPIN gene increase the risk of developing LOAD by causing a decline in immune function in the brain.It is expected that this result will contribute to the development of therapeutic agents by advancing the development of methods for predicting the risk of developing Alzheimer's disease and the elucidation of the pathological mechanism.
Paper information:[Molecular Medicine] A rare functional variant of SHARPIN predicts the inflammatory response and associates with increased risk of late-onset Alzheimer's disease
