Ten to 25% of people with late-onset Alzheimer's disease (AD) present with prominent executive deficits. Names such as frontal variant AD, executive prominent AD, and dysexecutive AD have been applied to this phenomenon. Little is known about traditional or genetic risk factors for dysexecutive AD. The overarching goal of this project is to further our understanding of the genetic architecture and clinical epidemiology of dysexecutive AD in the hopes of ultimately developing disease- modifying treatments. This project will leverage large-scale genome-wide genotype and sequence data and cognitive data collected on >17,000 participants across 19 collaborating studies. The investigators will use modern psychometric methods to co-calibrate cognitive data to develop scores on the same metric for memory and executive functioning. The investigators will use these scores to determine a continuous dysexecutive spectrum phenotype they have found to be highly heritable, with a pattern of heritability entirely distinct from that of AD. The investigators will leverage genome-wide genotype data for Aim 1. Five of the collaborating studies are prospective cohort studies with extensive cognitive and clinical data from >10,000 participants. The investigators will leverage these data for Aim 2. Several funding mechanisms are producing whole genome and whole exome sequencing data for people with AD. The investigators will leverage these data for Aim 3. Taken together, these investigations promise to improve what is known about dysexecutive AD, a highly heritable and devastating AD subtype. This work may identify genetic loci associated with risk for dysexecutive AD, which in turn may lead to development of drugs that could dramatically improve the lives of people with this condition.
The investigators propose to leverage extensive genetic, clinical, and cognitive data from 19 collaborating studies with >17,000 participants with Alzheimer's disease (AD) to further the understanding of dysexecutive AD, a devastating AD subtype. A series of genetic and epidemiological investigations are proposed. These investigations would dramatically increase the state of knowledge of this AD subtype, and may hasten the development of disease-modifying drugs.
|Yao, Xiaohui; Yan, Jingwen; Kim, Sungeun et al. (2016) Two-dimensional enrichment analysis for mining high-level imaging genetic associations. Brain Inform :|
|Du, Lei; Huang, Heng; Yan, Jingwen et al. (2016) Structured sparse CCA for brain imaging genetics via graph OSCAR. BMC Syst Biol 10 Suppl 3:68|
|Cholerton, Brenna; Larson, Eric B; Quinn, Joseph F et al. (2016) Precision Medicine: Clarity for the Complexity of Dementia. Am J Pathol 186:500-6|
|Mez, Jesse; Mukherjee, Shubhabrata; Thornton, Timothy et al. (2016) The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable. Neurobiol Aging 41:115-21|
|Hao, Xiaoke; Yao, Xiaohui; Yan, Jingwen et al. (2016) Identifying Multimodal Intermediate Phenotypes Between Genetic Risk Factors and Disease Status in Alzheimer's Disease. Neuroinformatics 14:439-52|
|Ebbert, Mark T W; Boehme, Kevin L; Wadsworth, Mark E et al. (2016) Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk. Alzheimers Dement 12:121-9|
|Hao, Xiaoke; Yan, Jingwen; Yao, Xiaohui et al. (2016) DIAGNOSIS-GUIDED METHOD FOR IDENTIFYING MULTI-MODALITY NEUROIMAGING BIOMARKERS ASSOCIATED WITH GENETIC RISK FACTORS IN ALZHEIMER'S DISEASE. Pac Symp Biocomput 21:108-19|
|Green, Robert C; Christensen, Kurt D; Cupples, L Adrienne et al. (2015) A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease. Alzheimers Dement 11:1222-30|
|Hohman, Timothy J; Samuels, Lauren R; Liu, Dandan et al. (2015) Stroke risk interacts with Alzheimer's disease biomarkers on brain aging outcomes. Neurobiol Aging 36:2501-8|
|Yao, Xiaohui; Yan, Jingwen; Kim, Sungeun et al. (2015) Two-dimensional Enrichment Analysis for Mining High-level Imaging Genetic Associations. Brain Inform Health (2015) 9250:115-124|
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