@article{d5bcc1a4cb0c49e4b92698afad29c1c4,
title = "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.",
keywords = "ADNI, Alzheimer's disease, Endophenotype, Pathway-based gene analysis, PiB-PET, Voxel-based analysis",
author = "Shanker Swaminathan and Li Shen and Risacher, {Shannon L.} and Yoder, {Karmen K.} and West, {John D.} and Sungeun Kim and Kwangsik Nho and Tatiana Foroud and Mark Inlow and Potkin, {Steven G.} and Huentelman, {Matthew J.} and Craig, {David W.} and Jagust, {William J.} and Koeppe, {Robert A.} and Mathis, {Chester A.} and Jack, {Clifford R.} and Weiner, {Michael W.} and Saykin, {Andrew J.}",
note = "Funding Information: Dr. Jack serves a consultant for Elan Corporation and GE Healthcare; receives research support from Pfizer, Inc., the NIH (NIA R01-AG11378 [PI] and U01 AG024904-01 [coinvestigator]), and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Foundation; and holds stock in GE Healthcare and Johnson & Johnson. Funding Information: Dr. Yoder is supported by NIAAA R21AA016901 [PI], NIDA R03DA024774 [PI], NIAAA R01AA017661 [coinvestigator], NIA P30AG010133-20 [coinvestigator, Neuroimaging Core], The Indiana State Department of Health [PI], the IUPUI Research Support Funds Grant [PI] and the Indiana CTSI Clinical Research Center, UL RR025761. Funding Information: Ms. Risacher receives support from the NIH (CTSI Pre-doctoral training grant, TL1 RR025759). Funding Information: Dr. Huentelman receives research support from the NIH/NINDS (R01 NS059873 [PI]) and the Arizona Alzheimer{\textquoteright}s Consortium. Funding Information: Samples from the National Cell Repository for AD (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the NIA, were used in this study. Additional support for data analysis was provided by NIA R01 AG19771 and P30 AG10133. The authors thank contributors, including the ADNI sites that collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. Funding Information: Dr. Jagust has served on a scientific advisory board for Genentech, Inc., Ceregene, Schering-Plough Corp., and Merck & Co; and receives research support from the NIH (AG027859 [PI], AG027984 [PI], and AG024904 [coinvestigator]) and from the Alzheimer{\textquoteright}s Association. Funding Information: Dr. Potkin serves on scientific advisory boards and speakers{\textquoteright} bureaus for and has received funding for travel and speaker honoraria from AstraZeneca, Bioline, Bristol Myers-Squibb, Cortex Pharmaceuticals, Inc., Dainippon Sumitomo Pharma, Janssen, Novartis, Merck Serono, Pfizer Inc., Otsuka Pharmaceutical Co., Ltd., Roche, and Minister Pharmaceuticals plc; serves on the editorial board of Brain Imaging and Behavior; conducts clinical procedures/imaging studies at the UCI Brain Imaging Center and Neuropsychiatric Clinical Research Division; and receives research support from the Transdisciplinary Imaging Genetics Center (TIGC) P20 RR020837, and the NIH (NCRR U24 RR021992 [PI], U01 AG032984 [PI], NCIRE AG036535 [coinvestigator]). Funding Information: Disclosures Dr. Shen receives support from the NIH (NIBIB R03 EB008674 [PI], NIBIB R03 EB008674S1 [PI], UL1RR025761 [PI of an Indiana CTSI pilot project]), and the NSF (IIS-1117335 [PI]). Funding Information: Dr. Nho receives support from the NIH (NLM T15LM07117 [postdoctoral trainee]). Funding Information: Dr. Craig has received research support from the Arizona Science Foundation, Arizona Alzheimer{\textquoteright}s Research Center, and the NIH (U01 HL086528 [PI] and R01 MH078151 [coinvestigator]). Funding Information: Dr. Foroud serves on the editorial boards of Psychiatric Genetics, Journal of Bone and Mineral Research, Behavior Genetics, Parkison- ism and Related Disorders, and Journal of Studies on Alcohol and Drugs; has served as a consultant for the Institute for Behavioral Genetics at the University of Colorado; and receives research support from the NIH (NIA 5U24AG021886 [PI], R01 AR047822 [PI], R01 NS037167 [PI], N01NS32357 [PI], U01AA014809 [PI], R01 CA141668 [PI], and P01 AG018397 [PI]), Families of Spinal Muscular Atrophy, the Muscular Dystrophy Association, HP Therapeutics Foundation, and CHDI Foundation (previously High Q Foundation). Funding Information: Dr. Koeppe receives research support from Elan Corporation and from the NIH (U01 AG024904 [coinvestigator], P01 NS15655 [coinvestigator], R01 HL079540 [coinvestigator], R01 DA022520 [coinvestigator], and R01 DA016423 [coinvestigator]).",
year = "2012",
month = mar,
doi = "10.1007/s11682-011-9136-1",
language = "English (US)",
volume = "6",
pages = "1--15",
journal = "Brain Imaging and Behavior",
issn = "1931-7557",
publisher = "Springer New York",
number = "1",
}