The goal of this proposal is to explore the relationship between neurofibrillary tangles and amyloid plaques, the hallmarks of Alzheimer's disease (AD) and the hippocampal response during a memory-taxing task in young (aged 45 to 60) participants who have a genetic risk for, but not yet any symptoms of AD. It is also to attempt to identify the earliest signs of the disease, and predictive factors for developing the disease. Volunteers, who have the APOE-4 allele, a known risk factor for AD, and their age-matched counterparts without APOE-4, will undergo functional magnetic resonance imaging while learning new associations, a task that previously has been shown to activate the hippocampus. These same subjects will undergo PET scans using FDDNP, a probe that attaches preferentially to amyloid plaques and neurofibrillary tangles and allows them to be imaged. The images will be """"""""unfolded"""""""", or portrayed in a two-dimensional field, using a computer application designed for that purpose. This will allow specific activation within the hippocampus to be identified and localized. The PET images and fMRI images will then be superimposed in such a way that it will be possible to determine whether localization of amyloid plaques and neurofibrillary tangles correspond to increases in signal intensity during memory tasks as seen in AD patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS045425-02
Application #
6838722
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Refolo, Lorenzo
Project Start
2003-09-30
Project End
2006-09-29
Budget Start
2004-09-30
Budget End
2005-09-29
Support Year
2
Fiscal Year
2004
Total Cost
$38,222
Indirect Cost
Name
University of California Los Angeles
Department
Psychiatry
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Braskie, Meredith N; Klunder, Andrea D; Hayashi, Kiralee M et al. (2010) Plaque and tangle imaging and cognition in normal aging and Alzheimer's disease. Neurobiol Aging 31:1669-78
Braskie, Meredith N; Small, Gary W; Bookheimer, Susan Y (2010) Vascular health risks and fMRI activation during a memory task in older adults. Neurobiol Aging 31:1532-42
Braskie, Meredith N; Small, Gary W; Bookheimer, Susan Y (2009) Entorhinal cortex structure and functional MRI response during an associative verbal memory task. Hum Brain Mapp 30:3981-92