Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer disease.
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.
Cai
Guiqing
G
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Atzmon
Gil
G
Naj
Adam C
AC
Beecham
Gary W
GW
Barzilai
Nir
N
Haines
Jonathan L
JL
Sano
Mary
M
Pericak-Vance
Margaret
M
Buxbaum
Joseph D
JD
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
D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
Arch Neurol. 1998 Sep;55(9):1185-91
9740112
Hum Mol Genet. 2006 Nov 15;15(22):3324-8
17035247
Am J Hum Genet. 2000 Jul;67(1):170-81
10827107
Genetics. 2000 Jun;155(2):945-59
10835412
J Biol Chem. 2008 Oct 31;283(44):29615-9
18650430
Bioinformatics. 2001 Aug;17(8):742-3
11524377
Neurology. 2006 Dec 26;67(12):2170-5
17190939
Am J Hum Genet. 2007 Sep;81(3):559-75
17701901
Hum Mol Genet. 2009 Oct 15;18(20):3987-96
19608551