Alzheimer's disease is characterized by progressive mental deterioration first manifested by memory loss; post-mortem specimens exhibit neuritic amyloid plaques and neurofibrillary tangles in the central nervous system. All familial Alzheimer's disease mutations studied to date involve the amyloid precursor protein (APP) processing, whose cleavage products include Abeta (Abeta), the major component of neuritic plaque cores. How Abeta participates in the pathophysiology of Alzheimer's disease is unknown. Based on transgenic mouse studies and data produced in the Malinow laboratory, Abeta causes synaptic changes before plaques or tangles become apparent. Using an in vitro model of Alzheimer's disease by transfecting organotypic hippocampal slices, over-expression of APP causes a post-synaptic alteration in AMPA receptor function. Using electrophysiologically-tagged AMPA receptors (AMPA-R), 2 photon laser scanning microscopy and immunofluorescence, this proposal will study the mechanisms underlying this synaptic depression, specifically AMPA-R trafficking, and the resultant Alzheimer's disease pathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS046829-02
Application #
6838723
Study Section
NST-2 Subcommittee (NST)
Program Officer
Talley, Edmund M
Project Start
2003-09-22
Project End
2006-09-21
Budget Start
2004-09-22
Budget End
2005-09-21
Support Year
2
Fiscal Year
2004
Total Cost
$29,078
Indirect Cost
Name
State University New York Stony Brook
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794