title: Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer disease.
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.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Guiqing
authors.initials: G
authors.lastname: Cai
authors.forename: Gil
authors.initials: G
authors.lastname: Atzmon
authors.forename: Adam C
authors.initials: AC
authors.lastname: Naj
authors.forename: Gary W
authors.initials: GW
authors.lastname: Beecham
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.forename: Margaret
authors.initials: M
authors.lastname: Pericak-Vance
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000072197:ADAM10 Protein; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
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