Aging and APOE genotype are two interacting risk factors for late onset Alzheimer's disease (AD). Oxidative stress is a major component of cellular aging. Lipid peroxidation, an important consequence of oxidative stress in brain, is attended by production of highly cytotoxic aldehydes that modify protein. The long term goal of this research project is to investigate mechanistic connections between aging and apoE metabolism in brain.
The Specific Aims are to examine (1) the chemical mechanisms by which products of lipid peroxidation covalently modify relevant protein targets, such as apoE and tau, (2) the biological consequences of these reactions, and (3) the extent to which they correlate with severity of AD. The proposed research will employ a combination of organic chemistry to synthesize congeners of products of lipid peroxidation, and immunochemistry to follow their reactions.
The Specific Aims will be examined in increasingly complex biological systems: neuroglial cell culture, hippocampal organotypic culture, and post mortem human brains with histopathologically verified diagnoses of AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG000774-04
Application #
6029724
Study Section
NST-2 Subcommittee (NST)
Project Start
1996-08-26
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pathology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212