Diabetes Mellitus, Brain Aging, and Alzheimer's Disease

Research project

Description

DESCRIPTION (provided by applicant): Diabetes mellitus (DM) and Alzheimer's
disease (AD) are expanding health problems. Recent evidence suggests that
these diseases may be related, at least in some patients, and that DM may
influence the initiation or progression of AD. Epidemiological and
biochemical data suggest the nature of specific metabolic alterations in brain
by which this may occur. The experiments described in this application will
test the hypothesis that age, inherited susceptibilities to environmental
factors, and DM combine to augment brain oxidative damage and
neurodegeneration in the absence of stroke. The Specific Aims proposed are
(1) to determine brain oxidative damage, AGE formation, neurodegeneration, and
complications of cerebrovascular disease in various models of experimental DM
in young and old rodents alone and in combination with models of age-related
oxidative damage to brain; (2) to determine whether interventions that
suppress oxidative stress and/or AGE formation are effective at limiting brain
oxidative damage, AGE formation, neurodegeneration, and cerebrovascuiar
disease in models developed in Specific Aim 1; and (3) determine oxidative
modifications on tau in cerebrospinal fluid (CSF) of probable AD patients to
develop biomarkers for use with experimental therapies such as those
investigated in Specific Aim 2.
The candidate's immediate career goal is to redirect his area of research from
cancer genetics and biology to the study of AD and related dementias.
Specifically, the candidate will be instructed in methods of analysis of the
chemical pathology of oxidized lipids and proteins in brain tissue and other
biological samples. He will apply his understanding of genetic models of
disease to studies that explore complex relations between genetic and
environmental factors in the generation of oxidative damage to brain. The
program developed in this application will allow him to integrate the training
and experience he has received to date with the neuropathology training he is
now undertaking to become a creative, productive, and independent
physician/scientist focused on the mechanisms of age-related dementing
illnesses.
StatusFinished
Effective start/end date7/15/026/30/05

Funding

  • National Institutes of Health: $166,060.00
  • National Institutes of Health: $169,422.00
  • National Institutes of Health: $172,884.00

Fingerprint

Brain Diseases
Diabetes Mellitus
Alzheimer Disease
Brain
Cerebrovascular Disorders
Genetic Research
Investigational Therapies
Genetic Models
Cerebrospinal Fluid
Dementia
Rodentia
Oxidative Stress
Theoretical Models
Biomarkers
Stroke
Pathology
Lipids
Health
Proteins

Keywords

  • Medicine(all)