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INPP5D mRNA Expression and Cognitive Decline in Japanese Alzheimer's Disease Subjects
Abstract:
Microglial dysfunction and inflammation have recently been shown to be related to the development of Alzheimer's disease (AD). Inositol polyphosphate-5-phosphatase (INPP5D) functions broadly as a negative regulator of immune signaling, and its locus was associated with development of AD in a large-scale genome-wide association study. Thus, we examined INPP5D mRNA expression and methylation rates of the CpG sites in the upstream region of INPP5D exon 1 in peripheral leukocytes in 50 AD and age- and sex-matched control subjects. INPP5D mRNA expression in AD subjects was significantly higher than that in control subjects (1.16±0.39 versus 1.0±0.23, p = 0.049) and was correlated with the Mini-Mental State Examination score (p = 0.002, r = 0.426) and the total score of the Alzheimer's Disease Assessment Scale (p < 0.001, r = -0.697). Methylation rates in the upstream region of INPP5D exon 1 were not significantly different between AD and control subjects (average rate: 3.5±3.0 versus 2.8±1.3, p = 0.551). Our results suggested that INPP5D mRNA expression was elevated in the early stage and decreased with cognitive decline in AD. INPP5D mRNA expression in leukocytes may be a useful biomarker for the early stage of AD.
Insights
Inositol polyphosphate-5-phosphatase (INPP5D) mRNA expression is elevated in early Alzheimer's disease (AD) and may serve as a biomarker. INPP5D levels correlate with cognitive decline in AD patients.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Microglial dysfunction and inflammation are implicated in Alzheimer's disease (AD) pathogenesis.
- Inositol polyphosphate-5-phosphatase (INPP5D) is a negative regulator of immune signaling and its gene locus is associated with AD risk.
- Altered INPP5D expression may contribute to AD development.
Purpose of the Study:
- To investigate INPP5D mRNA expression and DNA methylation in peripheral leukocytes of AD patients.
- To determine the correlation between INPP5D levels and cognitive function in AD.
- To evaluate INPP5D as a potential early biomarker for AD.
Main Methods:
- Quantified INPP5D mRNA expression and CpG site methylation in leukocytes from 50 AD patients and 50 matched controls.
- Utilized genome-wide association study data linking INPP5D locus to AD.
- Assessed correlations with Mini-Mental State Examination and Alzheimer's Disease Assessment Scale scores.
Main Results:
- INPP5D mRNA expression was significantly higher in AD subjects compared to controls (p=0.049).
- Elevated INPP5D expression correlated positively with cognitive function (MMSE score) and negatively with AD severity (ADAS scale score).
- No significant differences in methylation rates were observed between AD and control groups.
Conclusions:
- INPP5D mRNA expression is elevated in early-stage AD and decreases with cognitive decline.
- Leukocyte INPP5D mRNA expression shows potential as a sensitive biomarker for early AD detection.
- Further research is warranted to elucidate INPP5D's role in AD pathophysiology.
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