title: Alzheimer disease: modeling an Aβ-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 (Aβ) peptide. In past years, based on experimental studies, several hundreds of proteins have been shown to interfere with Aβ 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.
authors.affiliation: Inserm U1079, Rouen University, Institute for Research and Innovation in Biomedicine, Normandie University, Rouen, France.|National Reference Center for Young Alzheimer Patients (CNR-MAJ), Rouen, France.|Department of Research, Rouvray Psychiatric Hospital, Sotteville-lès-Rouen, France.|Normandy Center for Genomic Medicine and Personalized Medicine, Rouen, France.
authors.forename: D
authors.initials: D
authors.lastname: Campion
authors.affiliation: Inserm U1079, Rouen University, Institute for Research and Innovation in Biomedicine, Normandie University, Rouen, France.|Normandy Center for Genomic Medicine and Personalized Medicine, Rouen, France.
authors.forename: C
authors.initials: C
authors.lastname: Pottier
authors.affiliation: Inserm U1079, Rouen University, Institute for Research and Innovation in Biomedicine, Normandie University, Rouen, France.|National Reference Center for Young Alzheimer Patients (CNR-MAJ), Rouen, France.|Normandy Center for Genomic Medicine and Personalized Medicine, Rouen, France.|Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: G
authors.initials: G
authors.lastname: Nicolas
authors.affiliation: Inserm U1079, Rouen University, Institute for Research and Innovation in Biomedicine, Normandie University, Rouen, France.|Normandy Center for Genomic Medicine and Personalized Medicine, Rouen, France.
authors.forename: K
authors.initials: K
authors.lastname: Le Guennec
authors.affiliation: Inserm U1079, Rouen University, Institute for Research and Innovation in Biomedicine, Normandie University, Rouen, France.|Normandy Center for Genomic Medicine and Personalized Medicine, Rouen, France.
authors.forename: A
authors.initials: A
authors.lastname: Rovelet-Lecrux
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D030561:Databases, Nucleic Acid; D053263:Gene Regulatory Networks / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor