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.
Olgiati, P., Politis, A.m., Papadimitriou, G.n., DE RONCHI, D., Serretti, A. (2011). Genetics of late-onset Alzheimer's disease: update from the alzgene database and analysis of shared pathways. INTERNATIONAL JOURNAL OF ALZHEIMER'S DISEASE, 2011, 1-14 [10.4061/2011/832379].
Genetics of late-onset Alzheimer's disease: update from the alzgene database and analysis of shared pathways
DE RONCHI, DIANA;SERRETTI, ALESSANDRO
2011
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.