Dataset Information

No Associations Found between PGBD1 and the Age of Onset in Japanese Patients Diagnosed with Sporadic Alzheimer's Disease.

ABSTRACT: BACKGROUND/AIMS:PiggyBac transposable element derived 1 (PGBD1) encodes a molecule involved in epigenetic mechanisms that have been implicated in Alzheimer's disease (AD), and recent genome-wide association studies and meta-analyses have indicated that a single nucleotide polymorphism (SNP), rs3800324, in PGBD1 could be associated with AD and the age of onset. However, no Japanese patients were examined in these studies. The aim of the present study was to replicate the previous finding in Japanese AD cases. METHODS:We performed a case-control study (211 cases and 156 controls) to investigate the association between PGBD1 and Japanese AD using 4 tag SNPs including rs3800324. RESULTS:Single SNP and haplotype analysis showed no association between AD and age of onset, whereas genotypic and allelic frequencies of the ?4 of apolipoprotein E (APOE) showed an association with AD as expected. CONCLUSION:In Japanese AD, we observed no influence of PGBD1, as either a risk factor or a modifier, even though APOE was associated with AD in this population.

SUBMITTER: Ohnuma T

PROVIDER: S-EPMC3522449 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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No Associations Found between PGBD1 and the Age of Onset in Japanese Patients Diagnosed with Sporadic Alzheimer's Disease.

Ohnuma Tohru T Nakamura Tohru T Takebayashi Yuto Y Hanzawa Ryo R Kitazawa Maiko M Higashiyama Ryoko R Takeda Mayu M Thompson Katrin K Komatsu Miwa M Shimazaki Hiromi H Shibata Nobuto N Arai Heii H

Dementia and geriatric cognitive disorders extra 20120101 1

<h4>Background/aims</h4>PiggyBac transposable element derived 1 (PGBD1) encodes a molecule involved in epigenetic mechanisms that have been implicated in Alzheimer's disease (AD), and recent genome-wide association studies and meta-analyses have indicated that a single nucleotide polymorphism (SNP), rs3800324, in PGBD1 could be associated with AD and the age of onset. However, no Japanese patients were examined in these studies. The aim of the present study was to replicate the previous finding ...[more]

PMID: 23277782

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Project description:See Tijms and Visser (doi:10.1093/brain/awy113) for a scientific commentary on this article.Alzheimer's disease is preceded by a lengthy 'preclinical' stage spanning many years, during which subtle brain changes occur in the absence of overt cognitive symptoms. Predicting when the onset of disease symptoms will occur is an unsolved challenge in individuals with sporadic Alzheimer's disease. In individuals with autosomal dominant genetic Alzheimer's disease, the age of symptom onset is similar across generations, allowing the prediction of individual onset times with some accuracy. We extend this concept to persons with a parental history of sporadic Alzheimer's disease to test whether an individual's symptom onset age can be informed by the onset age of their affected parent, and whether this estimated onset age can be predicted using only MRI. Structural and functional MRIs were acquired from 255 ageing cognitively healthy subjects with a parental history of sporadic Alzheimer's disease from the PREVENT-AD cohort. Years to estimated symptom onset was calculated as participant age minus age of parental symptom onset. Grey matter volume was extracted from T1-weighted images and whole-brain resting state functional connectivity was evaluated using degree count. Both modalities were summarized using a 444-region cortical-subcortical atlas. The entire sample was divided into training (n = 138) and testing (n = 68) sets. Within the training set, individuals closer to or beyond their parent's symptom onset demonstrated reduced grey matter volume and altered functional connectivity, specifically in regions known to be vulnerable in Alzheimer's disease. Machine learning was used to identify a weighted set of imaging features trained to predict years to estimated symptom onset. This feature set alone significantly predicted years to estimated symptom onset in the unseen testing data. This model, using only neuroimaging features, significantly outperformed a similar model instead trained with cognitive, genetic, imaging and demographic features used in a traditional clinical setting. We next tested if these brain properties could be generalized to predict time to clinical progression in a subgroup of 26 individuals from the Alzheimer's Disease Neuroimaging Initiative, who eventually converted either to mild cognitive impairment or to Alzheimer's dementia. The feature set trained on years to estimated symptom onset in the PREVENT-AD predicted variance in time to clinical conversion in this separate longitudinal dataset. Adjusting for participant age did not impact any of the results. These findings demonstrate that years to estimated symptom onset or similar measures can be predicted from brain features and may help estimate presymptomatic disease progression in at-risk individuals.

Dataset Information

No Associations Found between PGBD1 and the Age of Onset in Japanese Patients Diagnosed with Sporadic Alzheimer's Disease.

Publications

No Associations Found between PGBD1 and the Age of Onset in Japanese Patients Diagnosed with Sporadic Alzheimer's Disease.

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