Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer Disease

• Published in: Neurobiology of aging 2012-02, Vol.33 (2), p.416-417.e3
• Main Authors: Cai, Guiqing, Atzmon, Gil, Naj, Adam C, Beecham, Gary W, Barzilai, Nir, Haines, Jonathan L, Sano, Mary, Pericak-Vance, Margaret, Buxbaum, Joseph D
• Format: Article
• Language: English
• Subjects: ADAM Proteins - genetics; ADAM10 Protein; Aged; Aged, 80 and over; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Amyloid Precursor Protein Secretases - genetics; Association; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetics; Humans; Internal Medicine; Medical sciences; Membrane Proteins - genetics; Middle Aged; Mutation; Mutation - genetics; Neurology; Polymorphism, Single Nucleotide - genetics; Prevalence; Rare variation; Risk Assessment; Risk Factors; United States - epidemiology; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2010.03.003

Abstract The Alzheimer amyloid protein precursor (APP) is subject to proteolysis by ADAM10 and ADAM17, precluding the formation of Aβ. Recently, coding variations in ADAM10 resulting in altered function have been reported in familial Alzheimer disease (AD). The authors carried out a large-scale (n = 576: Controls, 271; AD, 305) resequencing study of ADAM10 in sporadic AD. The results do not support a significant role for ADAM10 mutations in AD. The results also make it clear that the careful examination of ancestry required in any case-control comparison is especially true with rare variations, where even a very small number of variations might form the basis of scientific conclusions.