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Updated: Oct 13, 2026

Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model
Published on: July 26, 2011
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.
Abstract:
An ongoing controversy concerns the cellular distribution of the differentially spliced forms of the amyloid protein precursor (APP) mRNAs and changes in prevalence of these transcripts during Alzheimer's disease. In situ hybridization on serial sections was used to prove that most hippocampal pyramidal neurons contain both APP-751 and APP-695 mRNA species. The APP-751/APP-695 mRNA ratio is generally increased during Alzheimer's disease, as shown by RNA gel blot analysis. Moreover, there was a strong linear relation between the increase in APP-751/APP-695 mRNA ratio in pyramidal neurons and the density of senile plaques within the hippocampus and entorhinal cortex. Thus, the increase in APP-751/APP-695 mRNA provides a molecular marker for regional variations in plaque density between individuals diagnosed with Alzheimer's disease by the commonly used composite criteria.
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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