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PMID: 18813964 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta.

Neurogenetics ·Vol. 10 ·No. 1 ·2009-02-00 ·Pages 13-7

Kauwe JS, Wang J, Mayo K, Morris JC, Fagan AM, Holtzman DM, Goate AM

Abstract

The use of quantitative endophenotypes in genetic studies may provide greater power, allowing for the use of powerful statistical methods and a biological model for the effects of the disease-associated genetic variation. Cerebrospinal fluid (CSF) amyloid beta (Abeta) levels are promising endophenotypes for late-onset Alzheimer's disease (LOAD) and show correlation with LOAD status and Abeta deposition. In this study, we investigated 29 single nucleotide polymorphisms (SNPs) positive in AlzGene ( http://www.alzgene.org ) meta-analyses, for association with CSF Abeta levels in 313 individuals. This study design makes it possible to replicate reported LOAD risk alleles while contributing novel information about the mechanism by which they might affect that risk. Alleles in ACE, APOE, BDNF, DAPK1, and TF are significantly associated with CSF Abeta levels. In vitro analysis of the TF SNP showed a change in secreted Abeta consistent with the CSF phenotype and known Alzheimer's disease variants, demonstrating the utility of this approach in identifying SNPs that influence risk for disease via an Abeta-related mechanism.

MeSH Terms
Adult Aged Aged, 80 and over Alzheimer Disease/cerebrospinal fluid,genetics Amyloid beta-Peptides/cerebrospinal fluid Databases, Genetic Female Genetic Predisposition to Disease Genotype Humans Middle Aged Phenotype Polymorphism, Single Nucleotide Risk
Chemicals
Amyloid beta-Peptides
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kauwe John S K
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Wang Jun
Mayo Kevin
Morris John C
Fagan Anne M
Holtzman David M
Goate Alison M
References (23)
23 references, click to expand
  1. Assessment of Alzheimer's disease case-control associations using family-based methods.
    Neurogenetics. 2009 Feb;10(1):19-25 PMID: 18830724
  2. Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene and the rate of cognitive decline in Alzheimer's disease.
    Hum Mol Genet. 2007 Sep 15;16(18):2199-208 PMID: 17613540
  3. Mild cognitive impairment represents early-stage Alzheimer disease.
    Arch Neurol. 2001 Mar;58(3):397-405 PMID: 11255443
  4. Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A beta ); retards A beta aggregation, deposition, fibril formation; and inhibits cytotoxicity.
    J Biol Chem. 2001 Dec 21;276(51):47863-8 PMID: 11604391
  5. A high-throughput gene expression analysis technique using competitive PCR and matrix-assisted laser desorption ionization time-of-flight MS.
    Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3059-64 PMID: 12624187
  6. Haplotypes extending across ACE are associated with Alzheimer's disease.
    Hum Mol Genet. 2003 Apr 15;12(8):859-67 PMID: 12668609
  7. Pedigree disequilibrium tests for multilocus haplotypes.
    Genet Epidemiol. 2003 Sep;25(2):115-21 PMID: 12916020
  8. APOE epsilon4 allele is associated with reduced cerebrospinal fluid levels of Abeta42.
    Neurology. 2004 Jun 8;62(11):2116-8 PMID: 15184629
  9. FDA-preapproved drugs targeted to the translational regulation and processing of the amyloid precursor protein.
    J Mol Neurosci. 2004;24(1):129-36 PMID: 15314261
  10. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease.
    Nat Med. 1996 Aug;2(8):864-70 PMID: 8705854
  11. Measured haplotype analysis of the angiotensin-I converting enzyme gene.
    Hum Mol Genet. 1998 Oct;7(11):1745-51 PMID: 9736776
  12. Neuropathological and neuropsychological changes in "normal" aging: evidence for preclinical Alzheimer disease in cognitively normal individuals.
    J Neuropathol Exp Neurol. 1998 Dec;57(12):1168-74 PMID: 9862640
  13. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease.
    Ann Neurol. 1999 Mar;45(3):358-68 PMID: 10072051
  14. C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation.
    J Neurochem. 2006 Jan;96(1):218-27 PMID: 16305624
  15. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans.
    Ann Neurol. 2006 Mar;59(3):512-9 PMID: 16372280
  16. Reduction of iron-regulated amyloid precursor protein and beta-amyloid peptide by (-)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer's disease.
    J Neurochem. 2006 Apr;97(2):527-36 PMID: 16539659
  17. Neuropathology of older persons without cognitive impairment from two community-based studies.
    Neurology. 2006 Jun 27;66(12):1837-44 PMID: 16801647
  18. DAPK1 variants are associated with Alzheimer's disease and allele-specific expression.
    Hum Mol Genet. 2006 Sep 1;15(17):2560-8 PMID: 16847012
  19. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.
    Nat Genet. 2007 Jan;39(1):17-23 PMID: 17192785
  20. Abeta40 inhibits amyloid deposition in vivo.
    J Neurosci. 2007 Jan 17;27(3):627-33 PMID: 17234594
  21. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults.
    Arch Neurol. 2007 Mar;64(3):343-9 PMID: 17210801
  22. Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation.
    Ann Neurol. 2007 May;61(5):446-53 PMID: 17366635
  23. Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model.
    Ann Neurol. 2000 Jun;47(6):739-47 PMID: 10852539
Article Info
Journal
Neurogenetics
Abbr.
Neurogenetics
ISSN
1364-6753
DOI
10.1007/s10048-008-0150-4
Published
2009-02-00
Epub
2008-00-24
Pages
13-7
Language
English
Region
United States
NLM ID
9709714
PMCID
PMC2726757
Subset
IM
Grants
NIA NIH HHS · R01 AG016208-09S1 · United States
NIA NIH HHS · P01-AG03991 · United States
NINDS NIH HHS · P30 NS057105 · United States
NCRR NIH HHS · 1-KL2-RR024994-01 · United States
NIA NIH HHS · P01 AG003991-268686 · United States
NIA NIH HHS · P01-AG026276 · United States
NCRR NIH HHS · TL1 RR024995 · United States
NIA NIH HHS · P01 AG003991 · United States
NIA NIH HHS · P50 AG005681 · United States
NIA NIH HHS · P01 AG026276 · United States
NINDS NIH HHS · P30 NS057105-03 · United States
NCRR NIH HHS · UL1 RR024992 · United States
NIA NIH HHS · P50 AG005681-229010 · United States
NCRR NIH HHS · 1-TL1-RR024995-01 · United States
NIA NIH HHS · P50-AG05681 · United States
NCATS NIH HHS · UL1 TR000448 · United States
NIMH NIH HHS · T32 MH014677 · United States
NIA NIH HHS · R01-AG16208 · United States
NCRR NIH HHS · KL2 RR024994 · United States
PHS HHS · P30-N5057105 · United States
NIA NIH HHS · R01 AG016208-09 · United States
NIA NIH HHS · P01 AG026276-03 · United States
NIMH NIH HHS · T32 MH14677 · United States
NIA NIH HHS · R01 AG016208 · United States
External Links
PubMed source DOI: 10.1007/s10048-008-0150-4 PMC Full Text View journal details
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