PARP1 gene variation and microglial activity on [11C]PBR28 PET in older adults at risk for Alzheimer's disease
dc.contributor.author | Kim, Sungeun | |
dc.contributor.author | Nho, Kwangsik | |
dc.contributor.author | Risacher, Shannon L. | |
dc.contributor.author | Inlow, Mark | |
dc.contributor.author | Swaminathan, Shanker | |
dc.contributor.author | Yoder, Karmen K. | |
dc.contributor.author | Shen, Li | |
dc.contributor.author | West, John D. | |
dc.contributor.author | McDonald, Brenna C. | |
dc.contributor.author | Tallman, Eileen F. | |
dc.contributor.author | Hutchins, Gary D. | |
dc.contributor.author | Fletcher, James W. | |
dc.contributor.author | Farlow, Martin R. | |
dc.contributor.author | Ghetti, Bernardino | |
dc.contributor.author | Saykin, Andrew J. | |
dc.contributor.department | Radiology and Imaging Sciences, School of Medicine | en_US |
dc.date.accessioned | 2015-09-14T14:39:59Z | |
dc.date.available | 2015-09-14T14:39:59Z | |
dc.date.issued | 2013 | |
dc.description.abstract | Increasing evidence suggests that inflammation is one pathophysio-logical mechanism in Alzheimer's disease (AD). Recent studies have identified an association between the poly (ADP-ribose) polymerase 1 (PARP1) gene and AD. This gene encodes a protein that is involved in many biological functions, including DNA repair and chromatin remodeling, and is a mediator of inflammation. Therefore, we performed a targeted genetic association analysis to investigate the relationship between the PARP1 polymorphisms and brain micro-glial activity as indexed by [11C]PBR28 positron emission tomography (PET). Participants were 26 non-Hispanic Caucasians in the Indiana Memory and Aging Study (IMAS). PET data were intensity-normalized by injected dose/total body weight. Average PBR standardized uptake values (SUV) from 6 bilateral regions of interest (thalamus, frontal, parietal, temporal, and cingulate cortices, and whole brain gray matter) were used as endophenotypes. Single nucleotide polymorphisms (SNPs) with 20% minor allele frequency that were within +/− 20 kb of the PARP1 gene were included in the analyses. Gene-level association analyses were performed using a dominant genetic model with translocator protein (18-kDa) (TSPO) genotype, age at PET scan, and gender as covariates. Analyses were performed with and without APOE ε4 status as a covariate. Associations with PBR SUVs from thalamus and cingulate were significant at corrected p<0.014 and <0.065, respectively. Subsequent multi-marker analysis with cingulate PBR SUV showed that individuals with the “C” allele at rs6677172 and “A” allele at rs61835377 had higher PBR SUV than individuals without these alleles (corrected P<0.03), and individuals with the “G” allele at rs6677172 and “G” allele at rs61835377 displayed the opposite trend (corrected P<0.065). A previous study with the same cohort showed an inverse relationship between PBR SUV and brain atrophy at a follow-up visit, suggesting possible protective effect of microglial activity against cortical atrophy. Interestingly, all 6 AD and 2 of 3 LMCI participants in the current analysis had one or more copies of the “GG” allele combination, associated with lower cingulate PBR SUV, suggesting that this gene variant warrants further investigation. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Kim, S., Nho, K., Risacher, S. L., Inlow, M., Swaminathan, S., Yoder, K. K., … Saykin, A. J. (2013). PARP1 gene variation and microglial activity on [11C]PBR28 PET in older adults at risk for Alzheimer’s disease. Multimodal Brain Image Analysis : Third International Workshop, MBIA 2013, Held in Conjunction with MICCAI 2013, Nagoya, Japan, September 22, 2013 : Proceedings / Li Shen, Tianming Liu, Pew-Thian Yap, Heng Huang, Dinggang Shen, Carl-Fre., 8159, 150–158. http://doi.org/10.1007/978-3-319-02126-3_15 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/6829 | |
dc.language.iso | en_US | en_US |
dc.publisher | Springer | en_US |
dc.relation.isversionof | 10.1007/978-3-319-02126-3_15 | en_US |
dc.relation.journal | Multimodal Brain Image Anal | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Alzheimer's disease | en_US |
dc.subject | polymerase 1 gene | en_US |
dc.title | PARP1 gene variation and microglial activity on [11C]PBR28 PET in older adults at risk for Alzheimer's disease | en_US |
dc.type | Article | en_US |