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A novel correlation between the levels of beta-amyloid protein precursor and tau transcripts in the aged human brain
1Division of Biomedical Polymer Science, School of Medicine, Fujita Health University, Aichi, Japan.
Abstract:
beta-Amyloid protein precursor (APP) and tau are implicated in the pathogenesis of Alzheimer's disease. We quantified the levels of APP and tau transcripts in the three cortical regions of 38 aged human brains obtained from consecutive autopsied patients. The level of APP mRNA was directly proportional to that of tau mRNA to a remarkable extent, suggesting coordinate expression of the APP and tau genes, whereas much weaker correlations were noted among mRNAs encoding other neuronal proteins. From the previous data on the differential expression of APP and tau mRNAs, the levels of APP-751 and -695 mRNAs were calculated and found to be proportional to those of four-repeat and three-repeat tau mRNAs, respectively, whereas that of APP-770 mRNA was rather constant. These results suggest that the mRNA concentrations of APP isoforms are linked to those of tau isoforms in the aged human brain.
Insights
Alzheimer's disease involves beta-amyloid precursor protein (APP) and tau. Their mRNA levels correlate in aged human brains, suggesting coordinated gene expression is crucial for brain health.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease pathogenesis involves beta-amyloid precursor protein (APP) and tau.
- Understanding the relationship between APP and tau gene expression is critical for Alzheimer's research.
Purpose of the Study:
- To quantify the levels of APP and tau transcripts in three cortical regions of aged human brains.
- To investigate the correlation between APP and tau mRNA expression and their isoforms.
Main Methods:
- Quantification of APP and tau mRNA levels using transcript analysis.
- Analysis of mRNA concentrations for specific APP isoforms (APP-751, APP-695, APP-770) and tau isoforms (four-repeat and three-repeat).
- Statistical analysis to determine correlations between different mRNA levels.
Main Results:
- A strong direct proportionality was observed between the levels of APP mRNA and tau mRNA.
- Weaker correlations were found between APP/tau mRNAs and those of other neuronal proteins.
- APP-751 and APP-695 mRNA levels were proportional to four-repeat and three-repeat tau mRNAs, respectively.
- APP-770 mRNA levels remained relatively constant.
Conclusions:
- The findings suggest coordinate expression of APP and tau genes in the aged human brain.
- mRNA concentrations of APP isoforms are linked to those of tau isoforms.
- This coordinated expression may play a significant role in Alzheimer's disease pathogenesis.