Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

Steven P. Millard; Franziska Lutz; Ge Li; Douglas R. Galasko; Martin R. Farlow; Joseph F. Quinn; Jeffrey A. Kaye; James B. Leverenz; Debby Tsuang; Chang En Yu; Elaine R. Peskind; Lynn M. Bekris

doi:10.1016/j.neurobiolaging.2013.07.027

Association of cerebrospinal fluid Aβ₄₂ with A2M gene in cognitively normal subjects

Steven P. Millard
, Franziska Lutz
, Ge Li
, Douglas R. Galasko
, Martin R. Farlow
, Joseph F. Quinn
, Jeffrey A. Kaye
, James B. Leverenz
, Debby Tsuang
, Chang En Yu
, Elaine R. Peskind
, Lynn M. Bekris

Neurology

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

8 Scopus citations

Abstract

Low cerebrospinal fluid (CSF) Aβ₄₂ levels correlate with increased brain Aβ deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ₄₂ levels than non-carriers. The hypothesis of this investigation was that CSF Aβ₄₂ levels would correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ₄₂ levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5' and 3' regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ₄₂ levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ₄₂ levels in controls butnot in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ₄₂ levels.

Original language	English (US)
Pages (from-to)	357-364
Number of pages	8
Journal	Neurobiology of Aging
Volume	35
Issue number	2
DOIs	https://doi.org/10.1016/j.neurobiolaging.2013.07.027
State	Published - Feb 1 2014

Funding

This material is based on work supported in part by the US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program (Merit Review 1I01BX000531 ). It is also supported by National Institute of Health grants NS48595 , NS065070 , NS062684 , AG06781 , AG10845 , AG05136 , AG05133 , AG028383 , AG008017 , AG027224 , AG10124 , AG030653 , and K99 AG034214 / 5 R00 AG034214 .

Funders	Funder number
US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program	1I01BX000531
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	NS062684, AG10845, K99 AG034214 / 5 R00 AG034214, AG05136, AG028383, NS065070, NS48595, AG10124, AG030653, AG008017, AG05133, AG06781
National Institute of Aging	R01AG027224

Keywords

A2M
APOE
Alpha-2-Macroglobulin
Alzheimer's disease
Aβ
Cerebrospinal fluid

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

Access to Document

10.1016/j.neurobiolaging.2013.07.027

Cite this

@article{217784f5b5764dbf88dfcc271f5d4802,

title = "Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects",

abstract = "Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels would correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5' and 3' regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls butnot in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels.",

keywords = "A2M, APOE, Alpha-2-Macroglobulin, Alzheimer's disease, Aβ, Cerebrospinal fluid",

author = "Millard, \{Steven P.\} and Franziska Lutz and Ge Li and Galasko, \{Douglas R.\} and Farlow, \{Martin R.\} and Quinn, \{Joseph F.\} and Kaye, \{Jeffrey A.\} and Leverenz, \{James B.\} and Debby Tsuang and Yu, \{Chang En\} and Peskind, \{Elaine R.\} and Bekris, \{Lynn M.\}",

note = "Funding Information: This material is based on work supported in part by the US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program (Merit Review 1I01BX000531 ). It is also supported by National Institute of Health grants NS48595 , NS065070 , NS062684 , AG06781 , AG10845 , AG05136 , AG05133 , AG028383 , AG008017 , AG027224 , AG10124 , AG030653 , and K99 AG034214 / 5 R00 AG034214 .",

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AU - Millard, Steven P.

AU - Lutz, Franziska

AU - Li, Ge

AU - Galasko, Douglas R.

AU - Farlow, Martin R.

AU - Quinn, Joseph F.

AU - Kaye, Jeffrey A.

AU - Leverenz, James B.

AU - Tsuang, Debby

AU - Yu, Chang En

AU - Peskind, Elaine R.

AU - Bekris, Lynn M.

N1 - Funding Information: This material is based on work supported in part by the US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program (Merit Review 1I01BX000531 ). It is also supported by National Institute of Health grants NS48595 , NS065070 , NS062684 , AG06781 , AG10845 , AG05136 , AG05133 , AG028383 , AG008017 , AG027224 , AG10124 , AG030653 , and K99 AG034214 / 5 R00 AG034214 .

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels would correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5' and 3' regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls butnot in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels.

AB - Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels would correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5' and 3' regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls butnot in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels.

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