Genetics of Late-Onset Alzheimer's Disease : Update from the Alzgene Database and Analysis of Shared Pathways

Abstract EN

The genetics of late-onset Alzheimer's disease (LOAD) has taken impressive steps forwards in the last few years.

To date, more than six-hundred genes have been linked to the disorder.

However, only a minority of them are supported by a sufficient level of evidence.

This review focused on such genes and analyzed shared biological pathways.

Genetic markers were selected from a web-based collection (Alzgene).

For each SNP in the database, it was possible to perform a meta-analysis.

The quality of studies was assessed using criteria such as size of research samples, heterogeneity across studies, and protection from publication bias.

This produced a list of 15 top-rated genes: APOE, CLU, PICALM, EXOC3L2, BIN1, CR1, SORL1, TNK1, IL8, LDLR, CST3, CHRNB2, SORCS1, TNF, and CCR2.

A systematic analysis of gene ontology terms associated with each marker showed that most genes were implicated in cholesterol metabolism, intracellular transport of beta-amyloid precursor, and autophagy of damaged organelles.

Moreover, the impact of these genes on complement cascade and cytokine production highlights the role of inflammatory response in AD pathogenesis.

Gene-gene and gene-environment interactions are prominent issues in AD genetics, but they are not specifically featured in the Alzgene database.