Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease

M Goedert1

  • 1MRC Laboratory of Molecular Biology, Cambridge, UK.

The EMBO Journal
|December 1, 1987
PubMed

Insights

Researchers studied amyloid beta protein precursor mRNA in Alzheimer's disease (AD) patients. They found reduced mRNA in the frontal cortex of AD patients, suggesting neurons are the source of amyloid plaques.

Area of Science:

  • Neuroscience
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) is characterized by the accumulation of amyloid plaques.
  • The amyloid beta protein precursor (APP) gene encodes the protein fragment that forms these plaques.

Purpose of the Study:

  • To investigate the tissue and cellular distribution of APP mRNA in human brain tissues.
  • To compare APP mRNA levels in control and Alzheimer's disease (AD) brains.

Main Methods:

  • Isolated clones of the APP gene from an AD patient's frontal cortex cDNA library.
  • Utilized in situ hybridization to determine the cellular localization of APP mRNA.
  • Examined brain tissues from both control and AD patients.

Main Results:

  • APP mRNA was expressed at similar levels across all examined brain regions in controls.
  • A reduction in APP mRNA levels was observed in the frontal cortex of AD patients.
  • APP mRNA was localized to neuronal cell bodies (granule and pyramidal cells) in the hippocampus and cerebral cortex.
  • No specific labeling was found in glial or endothelial cells.

Conclusions:

  • Senile plaque amyloid likely originates from neurons.
  • APP mRNA expression is not limited to brain regions or cells exhibiting selective neuronal death in AD.
  • Neuronal expression of APP suggests a primary role in amyloid plaque formation within neurons.

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