During the last two decades many genes have been shown to cause autosomal dominant forms of early onset dementing illnesses. These rare disorders have provided enormous insight into the pathogenesis of more common variants of the same diseases. Several of the most promising new therapeutics are based on the Afi hypothesis, a hypothesis largely supported by the causative mechanisms of disease mutations in autosomal dominant families. As these putative therapeutics are tested in clinical trials there is a growing need to use the FAD kindreds both to understand the natural history of the earliest clinical and preclinical phases of the disease and to test the efficacy of the therapeutics in a setting, where if the Afi hypothesis is correct, they should have a dramatic effect on prognosis. The first step in this overarching goal is to bring together a network of centers to characterize a large series of FAD kindreds with known disease-causing mutations. The goal of the Genetics Core of the DIAN initiative is to provide genetic information and useful biological materials to the research community for the study of AD. We will collect blood samples for DMA extraction from all study participants (n=300). Since these individuals are part of FAD kindreds with known causative mutations we will screen each sample for the known mutation in that family and genotype all families for known disease modifying alleles such as APOE e4. Blood from each individual will be sent to NCRAD for transformation to develop lymphoblastoid cell lines that will provide the largest resource of cell lines from FAD kindreds with known disease-causing mutations anywhere in the world.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AG032438-04
Application #
8374474
Study Section
Special Emphasis Panel (ZAG1-ZIJ-1)
Project Start
Project End
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
4
Fiscal Year
2012
Total Cost
$8,319
Indirect Cost
$1,799
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Ringman, John M; Monsell, Sarah; Ng, Denise W et al. (2016) Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database. J Neuropathol Exp Neurol 75:284-90
Su, Yi; Blazey, Tyler M; Owen, Christopher J et al. (2016) Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group. PLoS One 11:e0152082
Jin, Yan; Su, Yi; Zhou, Xiao-Hua et al. (2016) Heterogeneous multimodal biomarkers analysis for Alzheimer's disease via Bayesian network. EURASIP J Bioinform Syst Biol 2016:12
Chatterjee, Pratishtha; Lim, Wei L F; Shui, Guanghou et al. (2016) Plasma Phospholipid and Sphingolipid Alterations in Presenilin1 Mutation Carriers: A Pilot Study. J Alzheimers Dis 50:887-94
Su, Yi; Vlassenko, Andrei G; Couture, Lars E et al. (2016) Quantitative hemodynamic PET imaging using image-derived arterial input function and a PET/MR hybrid scanner. J Cereb Blood Flow Metab :
Chen, Ling; Sun, Jianguo; Xiong, Chengjie (2016) A multiple imputation approach to the analysis of clustered interval-censored failure time data with the additive hazards model. Comput Stat Data Anal 103:242-249
Lee, Seonjoo; Viqar, Fawad; Zimmerman, Molly E et al. (2016) White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network. Ann Neurol 79:929-39
Bateman, Randall J; Benzinger, Tammie L; Berry, Scott et al. (2016) The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model. Alzheimers Dement :
Su, Yi; Blazey, Tyler M; Owen, Christopher J et al. (2016) Correction: Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group. PLoS One 11:e0163669
Babulal, Ganesh M; Ghoshal, Nupur; Head, Denise et al. (2016) Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels. Am J Geriatr Psychiatry 24:1095-1104

Showing the most recent 10 out of 74 publications