AGGREGATION/DEPOSITION OF B AMYLOID IN ALZHEIMER DISEASE

Project: Research project

Project Details

Description

The salient pathological feature of Alzheimer's Disease (AD) is the
presence of a high density of amyloid plaques in the brain tissue of AD
victims. The plaques are predominantly composed of human beta-amyloid
peptide (betaA4) a 39-42 mer whose neurotoxicity appears to be related to
its aggregation. While the exact origin of the betaA4 in these plaques
remains uncertain, betaA4 appears to be made by most if not all cells in
the CNS, and is present in normal human CSF at a concentration of 10.10M. The primary thrust of the present proposal is to explore the aggregation,
deposition and binding characteristics of low, physiological concentrations
of betaA4 (10,10M). The key to the present proposal is our development of
a novel radioiodinated ~A4 which will allow us for the first time to
examine the characteristics of this molecule and its related fragments at
concentrations similar to that found in normal human CSF. Using
physiological concentrations of the radioiodinated betaA4 we will examine;
the characteristics, kinetics and factors affecting I3A4 aggregation and
disaggregation in a tissue free system; the characteristics, kinetics and
factors affecting betaA4 deposition onto tissue sections of AD and normal
human brain; the characteristics of betaA4 binding to tissue sections of
adult rat brain and the neonatal rat; the characteristics and kinetics of
betaA4 binding to specific populations of cultured neurons and glia: and
the correlation between the in vitro toxicity of betaA4 aggregates and
their aggregation/disaggregation characteristics. These studies will provide an understanding of the characteristics of
betaA4 self-aggregation and deposition at physiological concentrations of
betaA4. Understanding the factors influencing the aggregation and
deposition of physiological concentrations of betaA4 should provide new
insight into the amyloidosis that occurs in AD. Since aggregates of betaA4
are neurotoxic to cells within the CNS, this work may lead to a new
understanding and treatment for the dementia in AD.
StatusFinished
Effective start/end date9/10/946/30/97

Funding

  • National Institutes of Health: $121,004.00
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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