Increasing evidence suggests that inflammation is one pathophysiological mechanism in Alzheimer's disease (AD). Recent studies have identified an association between the poly (ADP-ribose) polymerase 1 (PARP1) gene...
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ISBN:
(纸本)9783319021256
Increasing evidence suggests that inflammation is one pathophysiological 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 microglial 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 [11C]PBR28 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 [11C]PBR28 SUVs from thalamus and cingulate were significant at corrected p11C]PBR28 SUV showed that individuals withthe "C" allele at rs6677172 and "A" allele at rs61835377 had higher [11C]PBR28 SUV than individuals without these alleles (corrected P11C]PBR28 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 [ 11C]PBR28 SUV, suggesting that this gene variant warrants fu
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