Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
329268 | Neurobiology of Aging | 2011 | 5 Pages |
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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Authors
José Luis Vázquez-Higuera, Ana MartÃnez-GarcÃa, Pascual Sánchez-Juan, Eloy RodrÃguez-RodrÃguez, Ignacio Mateo, Ana Pozueta, Ana Frank, Fernando Valdivieso, José Berciano, MarÃa J. Bullido, Onofre Combarros,