Genetics of late-onset Alzheimer's disease: Update from the Alzgene database and analysis of shared pathways

Paolo Olgiati, Antonis Politis, George N. Papadimitriou, Diana De Ronchi, Alessandro Serretti

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number832379
JournalInternational Journal of Alzheimer's Disease
DOIs
Publication statusPublished - 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Clinical Neurology
  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Aging
  • Cellular and Molecular Neuroscience
  • Neurology

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