AI Article Synopsis
- Neurofibrillary tangles in Alzheimer's disease are linked to hyperphosphorylated tau protein, with Tau-tubulin kinase-1 (TTBK1) playing a key role in this process.
- A study genotyped nine SNPs in the TTBK1 gene in 645 Spanish AD patients and 738 healthy individuals, revealing specific SNPs associated with a reduced risk of AD.
- The findings suggest that TTBK1 could be an important genetic factor influencing tau phosphorylation and AD susceptibility.
Article Abstract
Neurofibrillary tangles, one of the characteristic neuropathological lesions found in Alzheimer's disease (AD) brains, are composed of abnormally hyperphosphorylated tau protein. Tau-tubulin kinase-1 (TTBK1) is a brain-specific protein kinase involved in tau phosphorylation at AD-related sites. We examined genetic variations of TTBK1 by genotyping nine haplotype tagging SNPs (htSNPs) (rs2104142, rs2651206, rs10807287, rs7764257, rs3800294, rs1995300, rs2756173, rs6936397, and rs6458330) in a group of 645 Spanish late-onset AD patients and 738 healthy controls. Using a recessive genetic model, minor allele homozygotes for rs2651206 in intron 1 (OR=0.50, p=0.0003), rs10807287 in intron 5 (OR=0.49, p=0.0002), and rs7764257 in intron 9 (OR=0.57, p=0.023), which are in strong linkage disequilibrium, had a lower risk of developing AD than subjects homozygotes and heterozygotes for the major allele. TTBK1 is a promising new candidate tau phosphorylation-related gene for AD risk.
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| http://dx.doi.org/10.1016/j.neurobiolaging.2009.12.021 | DOI Listing |
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