The imaging data set collected in the Dominantly Inherited Alzheimer Network (DIAN) participants to date represents a highly valuable resource for Alzheimers disease (AD) research. It has supported cross sectional analysis of PET and MRI data to develop a timeline for imaging biomarkers in autosomal dominant AD (ADAD). With this renewal application, the DIAN Imaging Core will continue to obtain and analyze longitudinal imaging data that is fully integrated with clinical, psychometric and cerebrospinal fluid (CSF) biomarkers, and will allow for mutation-specific genotype-phenotype analysis. The Core G: Imaging Core will be responsible for the acquisition, quality control, and analysis of the MRI and PET neuroimaging for DIAN. Carriers of AD-causing mutations and their non-carrier siblings are enrolled and followed in the Clinical Core through the international DIAN performance sites. Participants will undergo structural and functional MRI, amyloid PET, and metabolic PET imaging every 2 years, in conjunction with their clinical visits. The source imaging data and post-processed data will be available to collaborating and outside investigators and will be distributed by the Informatics and Biostatistics cores.
Specific aims are to: (1) Collect structural and functional MRI, amyloid PET and metabolic PET imaging. (2) Process image data, including segmentation and matched regions of interest across all modalities. (3) Follow up novel findings identified in DIAN participants, including (a) an imaging biomarker timeline in asymptomatic ADAD, (b) an early hypermetabolic phase of the disease, (c) similarities between decreased cerebral blood flow and hypometabolism near the onset of symptoms, and (d) a late stage with accelerated accumulation of microhemorrhages. (4) Conduct comparisons to late onset AD (LOAD), evaluate new imaging approaches, and perform exploratory genotypic-phenotypic analysis, to include imaging and pathology.

Public Health Relevance

Society will benefit from research that works to develop biomarkers, or indicators, of diseases such as Alzheimer disease. As researchers develop treatments and strategies to prevent Alzheimer disease, imaging biomarkers that help identify individuals that are at high risk for developing Alzheimer disease will be greatly beneficial to these individuals.

Agency
National Institute of Health (NIH)
Type
Multi-Year Funded Research Project Cooperative Agreement (UF1)
Project #
2UF1AG032438-07
Application #
8863374
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Xiong, Chengjie; Weng, Hua; Bennett, David A et al. (2014) Subsets of a large cognitive battery better power clinical trials on early stage Alzheimer's disease. Neuroepidemiology 43:131-9
Dobrowolska, Justyna A; Kasten, Tom; Huang, Yafei et al. (2014) Diurnal patterns of soluble amyloid precursor protein metabolites in the human central nervous system. PLoS One 9:e89998