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

Guiqing Cai; Gil Atzmon; Adam C. Naj; Gary W. Beecham; Nir Barzilai; Jonathan L. Haines; Mary Sano; Margaret Pericak-Vance; Joseph D. Buxbaum

doi:10.1016/j.neurobiolaging.2010.03.003

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

Guiqing Cai, Gil Atzmon, Adam C. Naj, Gary W. Beecham, Nir Barzilai, Jonathan L. Haines, Mary Sano, Margaret Pericak-Vance, Joseph D. Buxbaum

Medicine

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	416-417.e3
Journal	Neurobiology of Aging
Volume	33
Issue number	2
DOIs	https://doi.org/10.1016/j.neurobiolaging.2010.03.003
State	Published - Feb 2012

Keywords

Association
Genetics
Mutation
Rare variation

ASJC Scopus subject areas

Clinical Neurology
Geriatrics and Gerontology
Aging
General Neuroscience
Developmental Biology

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10.1016/j.neurobiolaging.2010.03.003

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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.",

keywords = "Association, Genetics, Mutation, Rare variation",

author = "Guiqing Cai and Gil Atzmon and Naj, {Adam C.} and Beecham, {Gary W.} and Nir Barzilai and Haines, {Jonathan L.} and Mary Sano and Margaret Pericak-Vance and Buxbaum, {Joseph D.}",

note = "Funding Information: This work was supported by grants from the National Institute on Aging of the National Institutes of Health ( AG010491 and AG002219 , as well as pilot award to GC from the Mount Sinai Alzheimer disease Research Center / AG005138 ). The longevity study was supported by AG027734 , AG018728 , RR012248 , DK020541 , and RR012248 and a grant from the Glenn Foundation . JDB is the G. Harold and Leila Y. Mathers Professor of Geriatrics and Adult Development. ",

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AU - Cai, Guiqing

AU - Atzmon, Gil

AU - Naj, Adam C.

AU - Beecham, Gary W.

AU - Barzilai, Nir

AU - Haines, Jonathan L.

AU - Sano, Mary

AU - Pericak-Vance, Margaret

AU - Buxbaum, Joseph D.

N1 - Funding Information: This work was supported by grants from the National Institute on Aging of the National Institutes of Health ( AG010491 and AG002219 , as well as pilot award to GC from the Mount Sinai Alzheimer disease Research Center / AG005138 ). The longevity study was supported by AG027734 , AG018728 , RR012248 , DK020541 , and RR012248 and a grant from the Glenn Foundation . JDB is the G. Harold and Leila Y. Mathers Professor of Geriatrics and Adult Development.

PY - 2012/2

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N2 - 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.

AB - 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.

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

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ASJC Scopus subject areas

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