DNA REPAIR IN AUTOPSY-PROVEN ALZHEIMER'S DISEASE

Project: Research project

Description

Evidence is accumulating of a DNA repair defect in non-neuronal cells of
Alz-heimer's patients. The hypothesis has been advanced that this defect
might be closely related to the cause of Alzheimer's disease. One of the
limitations of many investigations of living cells aimed at discovering the
etiology of Alzheimer's disease is the lack of a sufficient number of
non-neuronal cell lines available from pathologically-confirmed Alzheimer's
disease cases. This study will circumvent this problem by investigating
skin fibroblasts collected at autopsy from patients having
neuropathological investigations. This study will define the distribution
of DNA repair efficiency for 5 different forms of damage produced by 5
different agents (methyl methane sulfonate, x-irradiation, ultraviolet
light, mitomycin C and formaldehyde) in 3 age-matched populations, each of
about 50 patients, namely autopsy-proven Alzheimer's disease,
autopsy-proven non-Alzheimer brain disease (disease controls) and
autopsy-proven normal brains (normal controls). The techniques of
unscheduled DNA synthesis and alkaline elution sizing of DNA will be used.
This study will clearly define the relationship between DNA repair defects
and Alzheimer's disease. It will demonstrate whether DNA repair efficiency
is a potential cause of the neuronal degeneration, and whether it can be
used as a laboratory diagnostic tool for Alzheimer's disease. This study
will also provide 30 autopsy-confirmed Alzheimer's disease fibroblast lines
to the NIA Cell Repository, Camden, New Jersey, for use by the whole
scientific community.
StatusFinished
Effective start/end date6/1/8611/30/89

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

DNA Repair
Autopsy
Alzheimer Disease
Fibroblasts
DNA
Methane
Brain Diseases
Mitomycin
Formaldehyde
Cell Line
Brain
Population

ASJC

  • Medicine(all)