Amyloid pathway-based candidate gene analysis of [ 11 C]PiB-PET in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort

Shanker Swaminathan, Li Shen, Shannon L. Risacher, Karmen Yoder, John D. West, Sungeun Kim, Kwangsik Nho, Tatiana Foroud, Mark Inlow, Steven G. Potkin, Matthew J. Huentelman, David W. Craig, William J. Jagust, Robert A. Koeppe, Chester A. Mathis, Clifford R. Jack, Michael W. Weiner, Andrew Saykin

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Amyloid imaging with [ 11 C]Pittsburgh Compound-B (PiB) provides in vivo data on plaque deposition in those with, or at risk for, Alzheimer's disease (AD). We performed a gene-based association analysis of 15 quality-controlled amyloid-pathway associated candidate genes in 103 Alzheimer's Disease Neuroimaging Initiative participants. The mean normalized PiB uptake value across four brain regions known to have amyloid deposition in AD was used as a quantitative phenotype. The minor allele of an intronic SNP within DHCR24 was identified and associated with a lower average PiB uptake. Further investigation at whole-brain voxel-wise level indicated that non-carriers of the minor allele had higher PiB uptake in frontal regions compared to carriers. DHCR24 has been previously shown to confer resistance against beta-amyloid and oxidative stress-induced apoptosis, thus our findings support a neuroprotective role. Pathway-based genetic analysis of targeted molecular imaging phenotypes appears promising to help elucidate disease pathophysiology and identify potential therapeutic targets.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalBrain Imaging and Behavior
Volume6
Issue number1
DOIs
StatePublished - Mar 2012

Fingerprint

Genetic Association Studies
Amyloid
Neuroimaging
Alzheimer Disease
Alleles
Phenotype
Molecular Imaging
Brain
Genes
Single Nucleotide Polymorphism
Oxidative Stress
Apoptosis
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Therapeutics

Keywords

  • ADNI
  • Alzheimer's disease
  • Endophenotype
  • Pathway-based gene analysis
  • PiB-PET
  • Voxel-based analysis

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Behavioral Neuroscience
  • Radiology Nuclear Medicine and imaging

Cite this

Amyloid pathway-based candidate gene analysis of [ 11 C]PiB-PET in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. / Swaminathan, Shanker; Shen, Li; Risacher, Shannon L.; Yoder, Karmen; West, John D.; Kim, Sungeun; Nho, Kwangsik; Foroud, Tatiana; Inlow, Mark; Potkin, Steven G.; Huentelman, Matthew J.; Craig, David W.; Jagust, William J.; Koeppe, Robert A.; Mathis, Chester A.; Jack, Clifford R.; Weiner, Michael W.; Saykin, Andrew.

In: Brain Imaging and Behavior, Vol. 6, No. 1, 03.2012, p. 1-15.

Research output: Contribution to journalArticle

Swaminathan, S, Shen, L, Risacher, SL, Yoder, K, West, JD, Kim, S, Nho, K, Foroud, T, Inlow, M, Potkin, SG, Huentelman, MJ, Craig, DW, Jagust, WJ, Koeppe, RA, Mathis, CA, Jack, CR, Weiner, MW & Saykin, A 2012, 'Amyloid pathway-based candidate gene analysis of [ 11 C]PiB-PET in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort', Brain Imaging and Behavior, vol. 6, no. 1, pp. 1-15. https://doi.org/10.1007/s11682-011-9136-1
Swaminathan, Shanker ; Shen, Li ; Risacher, Shannon L. ; Yoder, Karmen ; West, John D. ; Kim, Sungeun ; Nho, Kwangsik ; Foroud, Tatiana ; Inlow, Mark ; Potkin, Steven G. ; Huentelman, Matthew J. ; Craig, David W. ; Jagust, William J. ; Koeppe, Robert A. ; Mathis, Chester A. ; Jack, Clifford R. ; Weiner, Michael W. ; Saykin, Andrew. / Amyloid pathway-based candidate gene analysis of [ 11 C]PiB-PET in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. In: Brain Imaging and Behavior. 2012 ; Vol. 6, No. 1. pp. 1-15.
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