This application is for the 5-year renewal of the program project, Healthy Aging and Senile Dementia (HASD), now in its 25th year. In this renewal, there is a continued focus on the clinical, psychometric, and neuropathologic correlates of dementia of the Alzheimer type (DAT) in comparison with healthy aging with a new thrust addressing preclinical Alzheimer's disease. Five interactive and supportive Cores are proposed: Core A: Administration provides administrative support to all components and assures progress in accomplishing program project goals. Core B: Clinical recruits, enrolls, psychometrically and clinically assesses subjects annually to supply all projects. Core C: Biostatistics oversees data management and provides statistical input to all Cores and projects. Core D: Neuropathology performs postmortem examinations for clinicopathological correlation for all studies and provides appropriate tissue and data to Projects as needed. Core E: Neuroimaging collects structural imaging data on our cohort to visualize change in anatomy associated with cognitive decline. Two new projects replace the current Projects 1 and 4, which have been completed. The new Project 1 (""""""""Preclinical AD predicts poststroke dementia"""""""" JC Morris) examines the relationship between the presence of amyloid in the brain (as measured by PET PIB) at time of stroke to the later development of dementia. The new Project 4 (""""""""Sequence variation in genes for biomarker proteins and age at onset of Alzheimer's Disease"""""""" AM Goate) uses CSF proteins as intermediate traits, or endophenotypes, to identify novel genetic risk factors for late onset DAT. Two current projects will continue in this application to extend their findings and explore new initiatives. Project 2 (""""""""Antecedent biomarkers of AD in CSF and plasma"""""""" DM Holtzman) examines whether markers in the CSF and plasma proteome can be combined to develop a more accurate determination of dementia risk in cognitively normal elderly individuals. Project 3 (""""""""Markers for DAT: Control, Variability and Personality,"""""""" D Balota) will develop cognitive markers as early indicators of DAT. Together, these projects and their supporting cores will focus on preclinical DAT in comparison with healthy brain aging and address the issue of detecting preclinical disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG003991-29
Application #
8215838
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4 (O4))
Program Officer
Hsiao, John
Project Start
1997-01-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
29
Fiscal Year
2012
Total Cost
$1,831,586
Indirect Cost
$626,595
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Day, Gregory S; Gordon, Brian A; Perrin, Richard J et al. (2018) In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease. Neurology 90:e896-e906
Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G et al. (2018) Tau Kinetics in Neurons and the Human Central Nervous System. Neuron 97:1284-1298.e7
Lewczuk, Piotr; Riederer, Peter; O'Bryant, Sid E et al. (2018) Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry 19:244-328
Vardarajan, Badri N; Barral, Sandra; Jaworski, James et al. (2018) Whole genome sequencing of Caribbean Hispanic families with late-onset Alzheimer's disease. Ann Clin Transl Neurol 5:406-417
Joseph-Mathurin, Nelly; Su, Yi; Blazey, Tyler M et al. (2018) Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease. Alzheimers Dement (Amst) 10:669-677
Pottier, Cyril; Zhou, Xiaolai; Perkerson 3rd, Ralph B et al. (2018) Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. Lancet Neurol 17:548-558
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
Del-Aguila, Jorge L; Fernández, Maria Victoria; Schindler, Suzanne et al. (2018) Assessment of the Genetic Architecture of Alzheimer's Disease Risk in Rate of Memory Decline. J Alzheimers Dis 62:745-756
Bonham, Luke W; Karch, Celeste M; Fan, Chun C et al. (2018) CXCR4 involvement in neurodegenerative diseases. Transl Psychiatry 8:73
Mishra, Shruti; Blazey, Tyler M; Holtzman, David M et al. (2018) Longitudinal brain imaging in preclinical Alzheimer disease: impact of APOE ?4 genotype. Brain 141:1828-1839

Showing the most recent 10 out of 911 publications