[Search for risk genes in Alzheimer's disease]

Area of Science:

• Neurogenetics
• Dementia Research
• Genomic Medicine

Background:

• Alzheimer's disease (AD) is the most prevalent neurodegenerative dementia.
• Genetic factors contribute significantly to AD susceptibility, accounting for up to 80% of risk.
• While rare familial cases involve mutations in APP, PSEN1, and PSEN2, sporadic AD genetics are more complex.

Purpose of the Study:

• To explore the complex genetic underpinnings of Alzheimer's disease.
• To highlight the advancements in identifying genetic risk factors for sporadic AD.
• To underscore the need for continued genetic research in AD.

Main Methods:

• Genome-wide association studies (GWAS) to identify common genetic risk factors.
• Whole exome sequencing (WES) to detect rare coding variants associated with AD risk.
• Analysis of genetic signals within biological pathways like lipid metabolism and immune response.

Main Results:

• Identification of 26 novel genetic risk factors for sporadic AD.
• Association of genetic signals with pathways including cholesterol and lipid metabolism, immune response, and endocytic trafficking.
• Discovery of rare coding variants in genes like TREM2, SORL1, and ABCA7 linked to AD risk.

Conclusions:

• Genomic approaches have substantially advanced the understanding of AD pathogenesis.
• Despite progress, the genetic architecture of sporadic AD remains incomplete.
• Further research is essential to fully elucidate the genetic basis of Alzheimer's disease.