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Analysis of amyloid precursor protein mRNAs in skin fibroblasts in Down's syndrome
K Urakami1, J Kataoka, A Okada
1Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Abstract:
We examined amyloid precursor protein (APP) mRNAs expression in skin fibroblasts from Down's syndrome (DS) patients of different ages to determine the time of occurrence of abnormal splicing. The ratio of APP770 + 751 mRNA to APP695 mRNA (APP770 + 751/695) was significantly increased in the young DS group and adult DS group compared with the age-matched control groups (p < 0.01, p < 0.05), but no significant increase was observed in the aged DS group compared with the age-matched control group. These findings suggest that metabolic abnormalities of the APP gene occur at a very early stage of DS, at a mean age of about 5 years. Therefore, metabolic abnormalities of the APP gene are considered to appear at a very young age also Alzheimer's disease (AD). In this study, we confirmed that examination of the APP gene in skin fibroblasts might be useful for early diagnosis of AD.
Insights
Abnormal splicing of the amyloid precursor protein (APP) gene occurs early in Down syndrome (DS), even in young patients. This finding suggests APP gene examination in skin fibroblasts may aid early Alzheimer
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Down syndrome (DS) is associated with an increased risk of early-onset Alzheimer's disease (AD).
- Amyloid precursor protein (APP) gene expression and splicing are implicated in the pathogenesis of both DS and AD.
Purpose of the Study:
- To investigate the temporal occurrence of abnormal APP mRNA splicing in skin fibroblasts from individuals with Down syndrome.
- To determine if APP gene abnormalities in fibroblasts could serve as an early diagnostic marker for AD-like changes.
Main Methods:
- Quantification of APP mRNA splicing variants (APP770 + 751/695 ratio) in skin fibroblasts.
- Comparison of APP mRNA splicing ratios between young, adult, and aged DS patient groups and age-matched controls.
Main Results:
- A significant increase in the APP770 + 751/695 mRNA ratio was observed in young and adult DS groups compared to controls (p < 0.01, p < 0.05).
- No significant difference in the APP ratio was found in the aged DS group compared to age-matched controls.
- These metabolic abnormalities of the APP gene appear to occur around 5 years of age in DS.
Conclusions:
- Metabolic abnormalities of the APP gene manifest at a very early stage in Down syndrome.
- These early APP gene changes in DS may mirror those seen in Alzheimer's disease.
- Analyzing APP gene expression in skin fibroblasts shows potential for early AD diagnosis.