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

Authors: Swaminathan, Shanker; Shen, Li; Risacher, Shannon L; Yoder, Karmen K; West, John D; Kim, Sungeun; Nho, Kwangsik; +12 Authors

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

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.

Country
United States
Keywords

Male, Aging, Biomedical and clinical sciences, Genotype, Biological Psychology, Neurodegenerative, Alzheimer's Disease, Medical and Health Sciences, Pathway-based gene analysis, Cohort Studies, Databases, Alzheimer Disease, Risk Factors, 80 and over, ADNI, Acquired Cognitive Impairment, Genetics, Psychology, Humans, 2.1 Biological and endogenous factors, Carbon Radioisotopes, Benzothiazoles, Aetiology, Polymorphism, Factual, Aged, Aniline Compounds, Gene Expression Profiling, Prevention, Voxel-based analysis, Psychology and Cognitive Sciences, Neurosciences, Health sciences, Brain, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Experimental Psychology, Alzheimer’s Disease Neuroimaging Initiative, Amyloidosis, Single Nucleotide, Brain Disorders, Thiazoles, Endophenotype, Phenotype, Positron-Emission Tomography, Neurological, Biomedical Imaging, Female, Dementia, PiB-PET

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    0
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
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NIH| FUNCTION BIRN
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  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U24RR021992-04
  • Funding stream: NATIONAL CENTER FOR RESEARCH RESOURCES
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NIH| MR HIPPOCAMPAL CHANGES IN ALZHEIMERS DISEASE AND AGING
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  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01AG011378-03
  • Funding stream: NATIONAL INSTITUTE ON AGING
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NIH| Genetic Analysis of Hip Fragility
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  • Funder: National Institutes of Health (NIH)
  • Project Code: 2R01AR047822-06A1
  • Funding stream: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
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NIH| FRONTOTEMPORAL DEMENTIA: GENES, IMAGES, AND EMOTIONS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P01AG019724-03
  • Funding stream: NATIONAL INSTITUTE ON AGING
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