Alzheimer disease: modeling an Aß-centered biological network.

ABSTRACT

In genetically complex diseases, the search for missing heritability is focusing on rare variants with large effect. Thanks to next generation sequencing technologies, genome-wide characterization of these variants is now feasible in every individual. However, a lesson from current studies is that collapsing rare variants at the gene level is often insufficient to obtain a statistically significant signal in case-control studies, and that network-based analyses are an attractive complement to classical approaches. In Alzheimer disease (AD), according to the prevalent amyloid cascade hypothesis, the pathology is driven by the amyloid beta (Aß) peptide. In past years, based on experimental studies, several hundreds of proteins have been shown to interfere with Aß production, clearance, aggregation or toxicity. Thanks to a manual curation of the literature, we identified 335 genes/proteins involved in this biological network and classified them according to their cellular function. The complete list of genes, or its subcomponents, will be of interest in ongoing AD genetic studies.