Genetic Variants of GSK3B are Associated with Biomarkers for Alzheimer's Disease and Cognitive Function
Artikel i vetenskaplig tidskrift, 2015

Background: Glycogen synthase kinase 3 beta (GSK3B) is the major kinase phosphorylating tau protein. Hyperphosphorylated tau is one of the hallmarks of Alzheimer's disease (AD). Despite extensive research, the role of GSK3B in AD pathogenesis is not fully understood. Objective: To evaluate possible associations between gene variants of GSK3B and risk of AD. Methods: Twelve GSK3B tag single-nucleotide polymorphisms (SNPs), together with the previously AD-associated rs334558, were analyzed in 583 AD patients and 673 controls. Analyses on single marker and haplotype levels were done to relate to risk of AD, Mini-Mental State Examination (MMSE) scores, and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau (P-tau(181)), and amyloid-beta (A beta(42)). Results: After correction for multiple testing, we found a number of associations of gene variants with CSF biomarker levels and cognitive function in the AD patients. Firstly, rs334558 was associated with elevated T-tau levels (p(c) = 0.04). Next, rs1154597 showed association with reducedA beta(42) levels (pc = 0.007). Lastly, rs3107669was associated with lower MMSE scores (p(c) = 0.03). In addition, one more SNP was nominally significantly associated with reduced A beta(42) levels and another was associated with reduced MMSE. Conclusion: We found GSK3B gene variants associated with cognitive function and CSF biomarkers T-tau and A beta(42). To our knowledge, this is the first time GSK3B has been associated with cognitive function or CSF biomarkers reflecting neuronal degeneration (T-tau) and brain amyloid load (A beta(42)). The regulation of GSK3B needs to be investigated further, to fully understand how these GSK3B gene variants are involved in AD pathogenesis.

single nucleotide polymorphism

association

biomarker

cerebrospinal fluid

glycogen synthase kinase 3 beta

Alzheimer's disease

Mini-Mental State Examination

tau

amyloid-beta peptide

gene

Författare

Petronella Kettunen

Göteborgs universitet

Susanna Larsson

Göteborgs universitet

Sandra Holmgren

Göteborgs universitet

Sandra Olsson

Göteborgs universitet

L. Minthon

Lunds universitet

Henrik Zetterberg

Göteborgs universitet

Kaj Blennow

Göteborgs universitet

Staffan Nilsson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Annica Sjölander

Göteborgs universitet

Journal of Alzheimers Disease

1387-2877 (ISSN)

Vol. 44 4 1313-1322

Ämneskategorier

Neurovetenskaper

DOI

10.3233/JAD-142025

PubMed

25420549

Mer information

Senast uppdaterat

2018-03-02