Dominantly inherited alzheimer network

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Project Title: Dominantly inherited alzheimer network
Project Number: 2UF1AG032438-07
Project web address: Follow on NIH
Organization: Washington University, United States, Missouri, SAINT LOUIS
Principal Investigators (PI): Bateman Randall J, US
 
Project Description:
Dominantly inherited Alzheimer's disease (AD) is an attractive model for study because the responsible mutations have known biochemical consequences that underlie the pathological basis of the disorder. The opportunity to determine the sequence of imaging and biomarker changes in asymptomatic gene carriers who are destined to develop AD may reveal critical information about the pathobiological cascade that culminates in symptomatic disease. Because the clinical and pathological phenotypes of autosomal dominant AD (ADAD) appear similar to those for the far more common late-onset sporadic AD, the nature and sequence of brain changes in ADAD also may be relevant for late-onset AD. However, individuals with ADAD are few and are geographically dispersed worldwide. In its initial funding period, the Dominantly Inherited Alzheimer's Network (DIAN) has established an international, multicenter registry of individuals (gene carriers and noncarriers; asymptomatic and symptomatic) who are biological adult children of a parent with a known causative mutation for AD in the amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genes in which the individuals are evaluated at entry and longitudinally thereafter with standard instruments to include the Uniform Data Set of the Alzheimer's Disease Centers, structural, functional, and amyloid imaging protocols developed by the Alzheimer's Disease Neuroimaging Initiative (ADNI), biological fluids (blood; CSF) in accordance with the ADNI protocols, and histopathological examination of cerebral tissue in individuals who come to autopsy also using ADNI protocols. In addition to establishing the DIAN registry, support was found for DIAN's major hypotheses examined. First, AD biomarker changes will identify MCs many years before these individuals develop symptomatic AD, thus supporting the concept of preclinical AD. Second, the initial biomarker changes in the preclinical stage of ADAD will involve Aß42, followed by changes related to neurodegeneration, followed by cognitive decline. Third, the clinical and neuropathological phenotypes of ADAD will be similar to, but not identical with, those of sporadic LOAD. Although data obtained in the initial budget period provide support for each of these hypotheses, all have yet to be confirmed with longitudinal data analyses. Hence, this application now emphasizes longitudinal data collection and analyses to truly appreciate how biomarkers change over time. This renewal application continues to address the 3 original DIAN hypotheses with increased emphasis on longitudinal data (increasing visit frequency for asymptomatic participants) and maintain current aims (maintenance of the established international DIAN registry of individuals (MCs and NCs, symptomatic and asymptomatic) with attention to preparing and adjusting for participants who participate in current and planned prevention trials. New scientific studies are planned; many funded independently of the DIAN grant and conducted within the DIAN infrastructure at no cost to DIAN.
 
Project Terms:
abbreviations address adult children affect age alzheimer's disease amendment amyloid beta-protein precursor amyloid imaging attention autopsy back base beta-site app cleaving enzyme 1 biochemical biological biological markers blood brain budgets cause of death cerebrum clinical cognitive cohort collection commit consultations cost counseling data data analyses data collection data set databases design development disease doctor of philosophy drug candidate effective therapy electronics exome experience family frequencies funding genes genetic genetic counseling genetic screening method glossary goals grant human resources image impaired cognition individual inherited inhibitor/antagonist instrument international intervention laboratories late onset alzheimer disease learning letters liquid substance maintenance mutation nature nerve degeneration neuroimaging observational study parents participant pharmaceutical preparations pharmacologic substance phenotype policies pre-clinical presenilin-1 prevent prevention programs protocols documentation ps2 protein (alzheimer-associated) public health relevance qualifying recruitment activity registries regrets repository research research infrastructure research personnel response science secondary prevention staging study models symptoms system technology therapy clinical trials time tissues united states united states national institutes of health user-friendly visit work
Project Title: Dominantly inherited alzheimer network
Project Number: 2UF1AG032438-07
Project web address: Follow on NIH
Organization: Washington University, United States, Missouri, SAINT LOUIS
Principal Investigators (PI): Bateman Randall J, US
 
Project Categories:
Natural Sciences
 
Other Information:
Fiscal Year: 2008
Project Start Date: 15 September 2008
Project End Date: 31 December 2020
Project program: Multi-Year Funded Research Project Cooperative Agreement
 
Project Funding Information:
Funding Mechanism: Non-SBIR/STTR RPGs
Year Funding Organization Total Funding, $
2014 NIH - National Institute On Aging $17,935,541
Project Title: Dominantly inherited alzheimer network
Project Number: 2UF1AG032438-07
Project web address: Follow on NIH
Organization: Washington University, United States, Missouri, SAINT LOUIS
Principal Investigators (PI): Bateman Randall J, US
 
Title FY Funding
Dian biostatistical core 2014 $305000
Dian clinical core 2014 $2898966
Dian administrative core 2014 $9449620
Dian neuropathology core 2014 $228750
Dian genetics core 2014 $256273
Dian biomarker core 2014 $842932
Dian imaging core 2014 $3039000
Dian informatics core 2014 $915000
Project Title: Dominantly inherited alzheimer network
Project Number: 2UF1AG032438-07
Project web address: Follow on NIH
Organization: Washington University, United States, Missouri, SAINT LOUIS
Principal Investigators (PI): Bateman Randall J, US
 
Project Title Organization FY Funding
Dominantly Inherited Alzheimer NetworkWashington University2016$99,908
Dominantly Inherited Alzheimer NetworkWashington University2014$17,935,541
Project Title: Dominantly inherited alzheimer network
Project Number: 2UF1AG032438-07
Project web address: Follow on NIH
Organization: Washington University, United States, Missouri, SAINT LOUIS
Principal Investigators (PI): Bateman Randall J, US
 
Project number Project title Principal investigator
There are no any related projects.
Project Title: Dominantly inherited alzheimer network
Project Number: 2UF1AG032438-07
Project web address: Follow on NIH
Organization: Washington University, United States, Missouri, SAINT LOUIS
Principal Investigators (PI): Bateman Randall J, US
 
Title Journal Year Country Rel
White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network. Ann Neurol 2016 united states
Quantitative hemodynamic PET imaging using image-derived arterial input function and a PET/MR hybrid scanner. J Cereb Blood Flow Metab 2016 united states
Amyloid Imaging, Cerebrospinal Fluid Biomarkers Predict Driving Performance Among Cognitively Normal Individuals. Alzheimer Dis Assoc Disord 2016 united states
Heterogeneous multimodal biomarkers analysis for Alzheimer's disease via Bayesian network. EURASIP J Bioinform Syst Biol 2016 germany
Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group. PLoS One 2016 united states
Neurological manifestations of autosomal dominant familial Alzheimer's disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). Lancet Neurol 2016 england
Changes in the plasma proteome at asymptomatic and symptomatic stages of autosomal dominant Alzheimer's disease. Sci Rep 2016 england
Multimodality Review of Amyloid-related Diseases of the Central Nervous System. Radiographics 2016 united states
BDNF Val66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer's disease. Brain 2016 england
Widespread white matter and conduction defects in PSEN1-related spastic paraparesis. Neurobiol Aging 2016 united states
Correction: Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group. PLoS One 2016 united states
The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model. Alzheimers Dement 2016 united states
Free and cued memory in relation to biomarker-defined abnormalities in clinically normal older adults and those at risk for Alzheimer's disease. Neuropsychologia 2015 england
Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN). Neuropathology 2015 australia
Quantitative analysis of PiB-PET with FreeSurfer ROIs. PLoS One 2013 united states
Pupil response biomarkers distinguish amyloid precursor protein mutation carriers from non-carriers. Curr Alzheimer Res 2013 united arab emirates
Parametric and non-parametric confidence intervals of the probability of identifying early disease stage given sensitivity to full disease and specificity with three ordinal diagnostic groups. Stat Med 2011 england