Genetics of late-onset Alzheimer's disease: update from the alzgene database and analysis of shared pathways.

Olgiati P, Politis AM, Papadimitriou GN, De Ronchi D, Serretti A.

Source

Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy.

Abstract

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.

PMID:: 22191060; [PubMed - in process]
PMCID: PMC3235576

Free PMC Article

Genetics of late-onset Alzheimer's dise... [Int J Alzheimers Dis. 2011] - PubMed - NCBI