Integrative genomics identifies APOE ε4 effectors in Alzheimer's disease

• Published in: Nature (London) Vol. 500; no. 7460; pp. 45 - 50
• Main Authors: Rhinn, Herve, Fujita, Ryousuke, Qiang, Liang, Cheng, Rong, Lee, Joseph H., Abeliovich, Asa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2013; Nature Publishing Group
• Subjects: 631/378/1689/1283; Age of Onset; Aged; Alleles; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Amyloid beta-Protein Precursor - metabolism; Apolipoprotein E4 - genetics; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cells, Cultured; Cerebral Cortex - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Endocytosis; Epistasis, Genetic; Female; Fibroblasts; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Genome, Human - genetics; Genome-Wide Association Study; Genomics; Heterozygote; Humanities and Social Sciences; Humans; Medical sciences; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; multidisciplinary; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurology; Neurons - drug effects; Neurons - metabolism; Phenotype; Piracetam - analogs & derivatives; Piracetam - pharmacology; Polymorphism, Genetic - genetics; Proteolysis - drug effects; Science; Transcriptome - genetics; Vertebrates: nervous system and sense organs; Human; Nervous system diseases; Cerebral cortex; Senescence; Alzheimer disease; Genetic variant; Central nervous system; Gene expression; Metabolism; Amyloid precursor protein; Encephalon; Endocytosis; Age of onset; Apolipoprotein E; Degenerative disease; Amyloid
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature12415

Late-onset Alzheimer’s disease (LOAD) risk is strongly influenced by genetic factors such as the presence of the apolipoprotein E ε4 allele (referred to here as APOE4 ), as well as non-genetic determinants including ageing. To pursue mechanisms by which these affect human brain physiology and modify...