Project: Research project

Project Details


This proposal represents a formalization of a group effort
researching the fundamental features of Alzheimer's disease.
Although broken down into five projects and a Core to facilitate
review, the application seeks support for a highly integrated study
of six major issues in Alzheimer's disease. Project #1 is
concerned with the definition of the potential significance of a
new protein recently discovered in the brains of patients with
Alzheimer's disease. The work planned includes determining
whether or not this protein occurs in the brains of patients with
other neurologic diseases, the possible detection of this protein in
spinal fluid and other tissues and fluids, and further
characterization of the nature and function of the protein.
Obtaining a cDNA probe for the gene for this protein and
molecular genetic studies are also planned. In Project #2,
antibodies raised to purified neurofibrilliary tangles are being
used to screen human brain expression vector cDNA libraries for
probes to components of the tangle. A series of probes is already
under investigation, and further screening is planned. The aim is
to determine in unambiguous fashion which epitopes are present in
purified tangles. In Project #3, the nature and source of amyloid
in neuritic plaques will come under study. New information
suggesting the presence of amyloid or amyloid precursors in
"primitive" neuritic plaques will be intensively investigated, and
biochemical and molecular techniques will be employed to
investigate the nature and source of amyloid fibrils. In Project
#4, cytoskeletal studies will be extended to animals and
peripheral fibroblasts from Alzheimer patients. In addition,
calcium and metabolic homeostasis will be investigated following
preliminary studies which clearly demonstrate abnormalities. In
Project #5, a coordinated study aimed at identifying early stages
of the cholinergic deficit in Alzheimer patients will be followed
by attempts at treatment. Using our large available patient
population, we will attempt to replicate the observation that a
rare complement C4 component occurs with high frequency in
patients with Alzheimer's disease.

We hope to further unravel some of the fundamental problems
apparent in research on Alzheimer's disease.
Effective start/end date1/1/014/30/00


  • Neurology
  • Clinical Neurology
  • Genetics
  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Molecular Biology
  • Cell Biology
  • Pathology and Forensic Medicine
  • Immunology


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