Relation of neuronal APP-751/APP-695 mRNA ratio and neuritic plaque density in Alzheimer's disease

S A Johnson1, T McNeill, B Cordell

  • 1Andrus Gerontology Center, University of Southern California, Los Angeles 90089.

Science (New York, N.Y.)
|May 18, 1990
PubMed

Insights

Alzheimer's disease alters amyloid precursor protein (APP) mRNA ratios in brain cells. Increased APP-751/APP-695 mRNA levels correlate with senile plaque density, serving as a disease marker.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Cellular distribution of amyloid precursor protein (APP) mRNA variants is debated.
  • Changes in APP mRNA prevalence during Alzheimer's disease (AD) are not fully understood.

Purpose of the Study:

  • To investigate the cellular distribution of APP-751 and APP-695 mRNA in the human hippocampus.
  • To determine if the ratio of these APP mRNA species changes in Alzheimer's disease.
  • To correlate changes in APP mRNA ratios with neuropathological hallmarks of AD.

Main Methods:

  • In situ hybridization on serial sections of human brain tissue.
  • RNA gel blot analysis to quantify mRNA levels.
  • Correlation analysis between mRNA ratios and senile plaque density.

Main Results:

  • Both APP-751 and APP-695 mRNA are present in most hippocampal pyramidal neurons.
  • The APP-751/APP-695 mRNA ratio is generally increased in Alzheimer's disease.
  • A strong linear relationship exists between the increased APP-751/APP-695 mRNA ratio and senile plaque density in the hippocampus and entorhinal cortex.

Conclusions:

  • The cellular distribution of APP mRNA variants is confirmed in hippocampal neurons.
  • Increased APP-751/APP-695 mRNA ratio serves as a molecular marker for regional plaque density in Alzheimer's disease.
  • This finding aids in understanding regional variations in AD neuropathology.

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