Association between Glycogen Synthase Kinase-3β Genetic Polymorphism and Late-Onset Alzheimer’s Disease
Abstract
Aberrant phosphorylated tau is the major component of the neurofibrillary tangles in Alzheimer's disease (AD) brains. Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates tau protein, and increased GSK-3beta expression has been associated with neurofibrillary tangles. Saitohin (STH) is a recently identified protein that shares tissue expression pattern with tau, and previous evidence in the Spanish population indicated that a polymorphism at codon 7 (Q7R) of the STH gene was associated with late-onset AD. Since both GSK-3beta and STH are related to tau, we examined the association between a polymorphism in the promoter region (-50) of the GSK-3beta gene and AD, either through an independent effect or through interaction with the STH (Q7R) polymorphism, in a well-defined group of 333 sporadic AD patients and 307 control subjects from Spain. The current study reveals that GSK-3beta (-50) TT genotype is associated with an increased risk (OR 1.99, p = 0.003) for late-onset (after the age of 72 years) AD. Our results indicate that both the GSK-3beta (-50) and STH (Q7R) polymorphisms increase the risk of late-onset (subjects >72 years) AD, although they appear to be independent and thus not to interact synergistically.
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Decreased phosphorylation of AKT (P-S473) and GSK3β (P-Ser9) has been observed in the brains of AD patients in comparison to age-matched controls.
“These findings are notable as decreased phosphorylation of AKT (P-S473) and GSK3β (P-Ser9) has been observed in the brains of AD patients in comparison to age-matched controls (Mateo et al., 2006; Steen et al., 2005).”
From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Mateo et al., 2006
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- Authors
- Mateo, I., Infante, J., Llorca, J., Rodríguez, E., Berciano, J., & Combarros, O.
- Affiliations
- Universidad de Cantabria (ES)
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 2006
- Volume
- 21
- Issue
- 4
- Pages
- 228-232
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W2042085359
- Cited by
- 53
- References
- 12
- Citations by year
- 2025: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 3 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 4
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Dementia and Geriatric Cognitive Disorders (publishedVersion)
- PubMed (publishedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- glycogen synthase kinase-3β, late-onset Alzheimer's disease, genetic susceptibility, tau phosphorylation, neurofibrillary tangles, gene-gene interaction, Spanish population
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Catchment Area, Health, Codon, Female, Genotype, Humans, Male, Middle Aged, Phosphorylation, Polymorphism, Genetic, Promoter Regions, Genetic, Spain, tau Proteins, Age of Onset, Glycogen Synthase Kinase 3, Apolipoprotein E4
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