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 #
5U19AG032438-06
Application #
8600223
Study Section
Special Emphasis Panel (ZAG1-ZIJ-1)
Project Start
Project End
2014-06-30
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
6
Fiscal Year
2014
Total Cost
$2,625
Indirect Cost
$1,809
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Su, Yi; Flores, Shaney; Hornbeck, Russ C et al. (2018) Utilizing the Centiloid scale in cross-sectional and longitudinal PiB PET studies. Neuroimage Clin 19:406-416
Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin et al. (2018) Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms. Alzheimers Dement 14:205-214
Kinnunen, Kirsi M; Cash, David M; Poole, Teresa et al. (2018) Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study. Alzheimers Dement 14:43-53
Lee, Seonjoo; Zimmerman, Molly E; Narkhede, Atul et al. (2018) White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer's disease. PLoS One 13:e0195838
Oxtoby, Neil P; Young, Alexandra L; Cash, David M et al. (2018) Data-driven models of dominantly-inherited Alzheimer's disease progression. Brain 141:1529-1544
Chhatwal, Jasmeer P; Schultz, Aaron P; Johnson, Keith A et al. (2018) Preferential degradation of cognitive networks differentiates Alzheimer's disease from ageing. Brain 141:1486-1500
Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank et al. (2018) Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease. Brain 141:1186-1200
Li, Zeran; Del-Aguila, Jorge L; Dube, Umber et al. (2018) Genetic variants associated with Alzheimer's disease confer different cerebral cortex cell-type population structure. Genome Med 10:43
Wang, Guoqiao; Berry, Scott; Xiong, Chengjie et al. (2018) A novel cognitive disease progression model for clinical trials in autosomal-dominant Alzheimer's disease. Stat Med 37:3047-3055
Vlassenko, Andrei G; Gordon, Brian A; Goyal, Manu S et al. (2018) Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease. Neurobiol Aging 67:95-98

Showing the most recent 10 out of 97 publications