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Three types of amyloid protein precursor mRNA in human brain: their differential expression in Alzheimer's disease
1Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
Abstract:
Three types of amyloid protein precursor (APP) mRNA, produced by alternative splicing, were detected by Northern blotting in human brains, both control and Alzheimer's disease. These mRNAs encode APP695 consisting of 695 amino acids, APP751 harboring a 56 amino acid insert homologous to a Kunitz-type trypsin inhibitor inside APP695, and APP770 containing an additional 19 amino acid insert. Another possible APP mRNA which encodes "APP714" containing a 19 amino acid insert was not found in brain samples tested. Quantitative analysis revealed that, although the relative expression levels of the three mRNAs were variable among individuals, there was no remarkable change in expression of APP695 and APP751 mRNAs in Alzheimer's disease compared with control, but that APP770 mRNA level was elevated significantly in Alzheimer's disease.
Insights
Alzheimer's disease brains show elevated levels of amyloid precursor protein (APP) mRNA variant APP770. Other APP mRNA types, APP695 and APP751, remained unchanged, suggesting specific isoform involvement in the disease.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Amyloid precursor protein (APP) is central to Alzheimer's disease pathology.
- Alternative splicing of APP mRNA produces various protein isoforms with potentially different functions.
Purpose of the Study:
- To investigate the expression levels of different amyloid precursor protein (APP) mRNA variants in Alzheimer's disease (AD) brains.
- To determine if specific APP mRNA isoforms are altered in AD compared to control brains.
Main Methods:
- Northern blotting was used to detect and quantify three main types of APP mRNA (APP695, APP751, APP770) in human brain samples.
- Quantitative analysis compared mRNA expression levels between AD and control groups.
Main Results:
- Three APP mRNA variants (APP695, APP751, APP770) were detected in human brain tissue.
- APP695 and APP751 mRNA levels showed no significant difference between AD and control brains.
- APP770 mRNA levels were significantly elevated in Alzheimer's disease brains compared to controls.
Conclusions:
- The study identified differential expression of APP mRNA isoforms in Alzheimer's disease.
- Elevated APP770 mRNA in AD brains suggests a potential role for this specific isoform in disease pathogenesis.