Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families

Karen T. Cuenco, Robert Friedland, Clinton T. Baldwin, Jianping Guo, Badri Vardarajan, Kathryn L. Lunetta, L. Adrienne Cupples, Robert C. Green, Charles DeCarli, L. A. Farrer Lindsay A.

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample. To examine the possibility that TTR SNPs affect specific components of the AD process, we tested association of these SNPs with four measures of neurodegeneration and cerebrovascular disease defined by magnetic resonance imaging (MRI) in a subset of 48 African American and 265 Caucasian sibships. Five of seven common SNPs and several haplotypes were significantly associated with hippocampal atrophy in the Caucasian sample. Two of these SNPs also showed marginal evidence for association in the African American sample. Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)249-256
Number of pages8
JournalNeurobiology of Aging
Volume32
Issue number2
DOIs
StatePublished - Feb 2011

Fingerprint

Prealbumin
Atrophy
Single Nucleotide Polymorphism
Alzheimer Disease
African Americans
Magnetic Resonance Imaging
Endophenotypes
Amyloidogenic Proteins
Cerebrovascular Disorders
Neuroimaging
Haplotypes
Animal Models
Population
Genes

Keywords

  • Alzheimer disease
  • Genetic association
  • Hippocampal atrophy
  • Magnetic resonance imaging
  • Transthyretin

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Cuenco, K. T., Friedland, R., Baldwin, C. T., Guo, J., Vardarajan, B., Lunetta, K. L., ... Farrer Lindsay A., L. A. (2011). Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families. Neurobiology of Aging, 32(2), 249-256. https://doi.org/10.1016/j.neurobiolaging.2009.02.014

Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families. / Cuenco, Karen T.; Friedland, Robert; Baldwin, Clinton T.; Guo, Jianping; Vardarajan, Badri; Lunetta, Kathryn L.; Cupples, L. Adrienne; Green, Robert C.; DeCarli, Charles; Farrer Lindsay A., L. A.

In: Neurobiology of Aging, Vol. 32, No. 2, 02.2011, p. 249-256.

Research output: Contribution to journalArticle

Cuenco, KT, Friedland, R, Baldwin, CT, Guo, J, Vardarajan, B, Lunetta, KL, Cupples, LA, Green, RC, DeCarli, C & Farrer Lindsay A., LA 2011, 'Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families', Neurobiology of Aging, vol. 32, no. 2, pp. 249-256. https://doi.org/10.1016/j.neurobiolaging.2009.02.014
Cuenco, Karen T. ; Friedland, Robert ; Baldwin, Clinton T. ; Guo, Jianping ; Vardarajan, Badri ; Lunetta, Kathryn L. ; Cupples, L. Adrienne ; Green, Robert C. ; DeCarli, Charles ; Farrer Lindsay A., L. A. / Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families. In: Neurobiology of Aging. 2011 ; Vol. 32, No. 2. pp. 249-256.
@article{b9e9f9a51efa4e6692a614ffb42b7741,
title = "Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families",
abstract = "In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample. To examine the possibility that TTR SNPs affect specific components of the AD process, we tested association of these SNPs with four measures of neurodegeneration and cerebrovascular disease defined by magnetic resonance imaging (MRI) in a subset of 48 African American and 265 Caucasian sibships. Five of seven common SNPs and several haplotypes were significantly associated with hippocampal atrophy in the Caucasian sample. Two of these SNPs also showed marginal evidence for association in the African American sample. Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis.",
keywords = "Alzheimer disease, Genetic association, Hippocampal atrophy, Magnetic resonance imaging, Transthyretin",
author = "Cuenco, {Karen T.} and Robert Friedland and Baldwin, {Clinton T.} and Jianping Guo and Badri Vardarajan and Lunetta, {Kathryn L.} and Cupples, {L. Adrienne} and Green, {Robert C.} and Charles DeCarli and {Farrer Lindsay A.}, {L. A.}",
year = "2011",
month = "2",
doi = "10.1016/j.neurobiolaging.2009.02.014",
language = "English (US)",
volume = "32",
pages = "249--256",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families

AU - Cuenco, Karen T.

AU - Friedland, Robert

AU - Baldwin, Clinton T.

AU - Guo, Jianping

AU - Vardarajan, Badri

AU - Lunetta, Kathryn L.

AU - Cupples, L. Adrienne

AU - Green, Robert C.

AU - DeCarli, Charles

AU - Farrer Lindsay A., L. A.

PY - 2011/2

Y1 - 2011/2

N2 - In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample. To examine the possibility that TTR SNPs affect specific components of the AD process, we tested association of these SNPs with four measures of neurodegeneration and cerebrovascular disease defined by magnetic resonance imaging (MRI) in a subset of 48 African American and 265 Caucasian sibships. Five of seven common SNPs and several haplotypes were significantly associated with hippocampal atrophy in the Caucasian sample. Two of these SNPs also showed marginal evidence for association in the African American sample. Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis.

AB - In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample. To examine the possibility that TTR SNPs affect specific components of the AD process, we tested association of these SNPs with four measures of neurodegeneration and cerebrovascular disease defined by magnetic resonance imaging (MRI) in a subset of 48 African American and 265 Caucasian sibships. Five of seven common SNPs and several haplotypes were significantly associated with hippocampal atrophy in the Caucasian sample. Two of these SNPs also showed marginal evidence for association in the African American sample. Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis.

KW - Alzheimer disease

KW - Genetic association

KW - Hippocampal atrophy

KW - Magnetic resonance imaging

KW - Transthyretin

UR - http://www.scopus.com/inward/record.url?scp=78649850501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649850501&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2009.02.014

DO - 10.1016/j.neurobiolaging.2009.02.014

M3 - Article

C2 - 19328595

AN - SCOPUS:78649850501

VL - 32

SP - 249

EP - 256

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

IS - 2

ER -