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.
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Increased INPP5D levels associated with inheritance of the common variant rs35349669 confer increased risk for late-onset sporadic Alzheimer's disease.
“Current evidence suggests that increased INPP5D levels associated with inheritance of the common variant rs35349669 confer increased risk for LOAD.7”
From Microglial <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [7]
The rs35349669 SNP confers AD risk.
“the rs35349669 single nucleotide polymorphism (SNP) confers AD risk,7”
From Microglial <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [7]
Variant rs35349669 is proposed to confer increased risk for AD, and rs61068452 is proposed to confer protection.
“While variant rs35349669 is proposed to confer increased risk for AD, rs61068452 is proposed to confer protection [166, 167].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [166]
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“This result was not predicted by the apparent effect of the common INPP5D polymorphisms, given that the rs35349669 single nucleotide polymorphism (SNP) confers AD risk, 7 while rs61068452 is apparently protective against AD.”
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<i>INPP5D</i> deficiency attenuates amyloid pathology in a mouse model of Alzheimer's disease
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- Authors
- Yoshino, Y., Yamazaki, K., Ozaki, Y., Sao, T., Yoshida, T., Mori, T., Mori, Y., Ochi, S., Iga, J.-I., & Ueno, S.-I.
- Affiliations
- Ehime University (JP)
- Corresponding author
- Iga, Jun-Ichi
- ORCID
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2017-06-05
- Volume
- 58
- Issue
- 3
- Pages
- 687-694
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2610941844
- Cited by
- 41
- References
- 6
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 9 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 2
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15K09808)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- INPP5D, inositol polyphosphate 5-phosphatase
- MeSH terms
- Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases, Mental Status and Dementia Tests, Aged, Alzheimer Disease, Female, Humans, Male, RNA, Messenger, Severity of Illness Index, Biomarkers, Gene Expression, CpG Islands, DNA Methylation, Cognitive Dysfunction
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