title: Genetics of late-onset Alzheimer's disease: update from the alzgene database and analysis of shared pathways.
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.
authors.affiliation: Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Olgiati
authors.forename: Antonis M
authors.initials: AM
authors.lastname: Politis
authors.forename: George N
authors.initials: GN
authors.lastname: Papadimitriou
authors.forename: Diana
authors.initials: D
authors.lastname: De Ronchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti