Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Abstract:
Clones for the amyloid beta protein precursor gene were isolated from a cDNA library prepared from the frontal cortex of a patient who had died with a histologically confirmed diagnosis of Alzheimer's disease; they were used to investigate the tissue and cellular distribution of amyloid beta protein precursor mRNA in brain tissues from control patients and from Alzheimer's disease patients. Amyloid beta protein precursor mRNA was expressed in similar amounts in all control human brain regions examined, but a reduction of the mRNA level was observed in the frontal cortex from patients with Alzheimer's disease. By in situ hybridization amyloid beta protein precursor mRNA was present in granule and pyramidal cell bodies in the hippocampal formation and in pyramidal cell bodies in the cerebral cortex. No specific labelling of glial cells or endothelial cells was found. The same qualitative distribution was observed in tissues from control patients and from patients with Alzheimer's disease. Senile plaque amyloid thus probably derives from neurones. The tissue distribution of amyloid beta protein precursor mRNA and its cellular localization demonstrate that its expression is not confined to the brain regions and cells that exhibit the selective neuronal death characteristic of Alzheimer's disease.
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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