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- W2037581579 abstract "Mitochondria, the location of the ATP generating electron transport chain (ETC), contain multiple copies of a circular genome 16569 bases in length. It is accepted that mitochondrial function is disrupted in the brains of AD patients. However, the mitochondria's exact role is not known. For example, senile plaques aggregate within the mitochondria of AD patients, but it is not known if this aggregation is a cause or effect of mitochondrial dysfunction, and what, if any, role the mitochondrial genome has in the development of AD. Several groups have attempted to identify mitochondrial SNPs and/or haplotypes associated with AD, but with limited success. Approximately 300 individuals from the Cache County Aging Study on Memory Health and Aging were selected and their mitochondrial genomes sequenced. Since mitochondria are maternally inherited it is possible to impute mitochondrial genomes based on shared maternal lineages. Following construction of a haplotype network we used an evolution-based haplotype analysis method, TreeScan, and a permutation based multiple test correction to identify specific haplotypes associated with AD case control status. Using these methods it is possible to identify specific variants that differ between haplotypes and thus identify variants driving the association. Our dataset consisted of 285 individuals with full mitochondrial genome sequences, an additional 723 with imputed sequences for a total of 1008 total individuals, consisting of 249 unique haplotypes. After multiple test correction two different haplogroups (groups of haplotypes) showed evidence of decreased AD incidence with p-values of 0.0361 (30 individuals, 11 haplotypes) and 0.0381 (29 individuals, 9 haplotypes). The majority of the haplotypes in these two groups were H6a1a/b. Strikingly, none of the individuals in either of the groups had AD despite having mean ages of 79.62 (median: 79.5) and 79.48 (median: 79.42) years, respectively. Specific mitochondrial variants had significant association with AD control status in our dataset. Our results are especially impressive given an average age of 79 in the two groups showing association. The specific variants, which define these two haplogroups, will be analyzed to determine how they could provide protection against AD." @default.
- W2037581579 created "2016-06-24" @default.
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- W2037581579 date "2012-07-01" @default.
- W2037581579 modified "2023-09-27" @default.
- W2037581579 title "O3-11-05: Mitochondrial variation associated with decreased Alzheimer's disease incidence in the Cache County Study on Memory Health and Aging" @default.
- W2037581579 doi "https://doi.org/10.1016/j.jalz.2012.05.1204" @default.
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