Alzheimer's disease genetics current status and future perspectives

Area of Science:

• Neurogenetics
• Genomic Epidemiology

Background:

• Alzheimer's disease (AD) pathogenesis is significantly influenced by genetic factors.
• Decades of research identified four established AD genes (APP, PSEN1, PSEN2, APOE) and numerous potential susceptibility loci.
• Genome-wide association studies (GWAS) add complex data to AD genetic research.

Purpose of the Study:

• To facilitate the evaluation and interpretation of AD genetic association study findings.
• To create a centralized database (AlzGene) for AD genetic association studies.
• To perform meta-analyses on polymorphisms with sufficient genotype data.

Main Methods:

• Systematic screening and summarization of scientific literature for eligible AD genetic studies.
• Development and utilization of the AlzGene database (http://www.alzgene.org).
• Allele-based meta-analyses of polymorphisms from eligible studies.

Main Results:

• The AlzGene database currently highlights over 20 potential AD genes.
• Meta-analyses revealed consistent AD risk effects for genetic variants in ACE, CHRNB2, GAB2, and TF, in addition to APOE.
• These findings are supported by follow-up analyses in over 1300 AD families across diverse study designs.

Conclusions:

• The study identifies key genetic variants (ACE, CHRNB2, GAB2, TF) contributing to Alzheimer's disease risk.
• The AlzGene database and meta-analysis approach provide powerful tools for unraveling AD's genetic underpinnings.
• Consistent genetic risk factors beyond APOE are crucial for understanding AD pathogenesis.