Tau polymorphisms are not associated with Alzheimer's disease

Kwon, Jennifer M.; Nowotny, Petra; Shah, Purvi K.; Chakraverty, Sumi; Norton, Joanne; Morris, John C.; Goate, Alison M.

doi:10.1016/s0304-3940(00)00972-1

Cited by 32 publications

(13 citation statements)

References 18 publications

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“…A polymorphism in intron 11 [125] or exon 7 [126] in the tau combined with at least one APOE Â4 allele was associated with an increased risk for AD. However, tau exon 2 polymorphism was not associated with AD [127].…”

Section: Taumentioning

confidence: 82%

Candidate Gene Association Studies in Sporadic Alzheimer’s Disease

Combarros

Alvarez-Arcaya²,

Sánchez-Guerra³

et al. 2002

Dement Geriatr Cogn Disord

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The genetics of Alzheimer’s disease (AD) is complex. Three genes (amyloid precursor protein, presenilin 1 and presenilin 2) have been described in the relatively rare, early-onset, autosomal dominant familial form of AD. In the common, non-familial (sporadic) late-onset AD, the major known genetic risk factor is the Ε4 allele of the apolipoprotein E (APOE) gene. However, at least half of the people who develop AD do not carry this allele, and not all people who do carry this allele develop AD even if they live to an old age. Therefore, approximately 30 other candidate genes involving a protein in a critical pathway in the pathogenesis of disease (principally interaction with amyloid-β, oxidative stress and inflammation/apoptosis) have been considered as risk factors for sporadic AD. Then these genes have been sequenced in search of genetic variability or polymorphisms, and each putative polymorphism has been reported to alter the risk of AD either directly or by an interaction with the APOE Ε4 allele. However, positive-association studies with these candidate genes have not been consistently confirmed.

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Section: Taumentioning

confidence: 82%

Candidate Gene Association Studies in Sporadic Alzheimer’s Disease

Combarros

Alvarez-Arcaya²,

Sánchez-Guerra³

et al. 2002

Dement Geriatr Cogn Disord

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“…Mutations in the human TAU gene have been linked to FTD [2,3] , but no TAU mutations have been identifi ed in AD patients. Beside the known mutations, several polymorphic sites have been identifi ed in the TAU gene but association studies have reported confl icting results [15,16,23,42,[47][48][49] . Since series of these common polymorphisms in the TAU gene are in complete linkage disequilibrium, two separate haplotypes, H1 and H2, have been defi ned.…”

Section: Discussionmentioning

confidence: 99%

<i>TAU</i> Haplotype and the <i>Saitohin</i> Q7R Gene Polymorphism Do Not Influence CSF Tau in Alzheimer’s Disease and Are Not Associated with Frontotemporal Dementia or Parkinson’s Disease

Johansson

Zetterberg²,

Håkansson³

et al. 2005

Neurodegener Dis

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Background: Recent studies have described Saitohin(STH), a gene located in the human TAU gene. The corresponding protein shows a similar tissue expression to tau, which is involved in many neurodegenerative disorders including Alzheimer’s disease (AD), frontotemporal dementia (FTD) and Parkinson’s disease (PD). A single nucleotide polymorphism in the STH gene has been suggested to be involved in sporadic AD and is in complete linkage disequilibrium with the TAU haplotype H1. Objective: A case-control study was performed to further explore the possible involvement of the STH Q7R polymorphism and the extended TAU haplotype in AD, FTD or PD. Methods: Patients with AD (n = 398), FTD (n = 96) and PD (n = 105), and controls (n = 186) were genotyped for the STH polymorphism and/or the TAU haplotype. Genotype data were related to levels of total-tau, phospho-tau and Aβ_1–42 in cerebral spinal fluid (CSF) in more than 300 AD patients and to an amount of senile plaques and neurofibrillary tangles in the frontal cortex and hippocampus in patients with autopsy-confirmed AD. Results: The STH Q7R polymorphism and the TAU haplotype were in complete linkage disequilibrium in all patients (AD and FTD) and controls investigated for both genes. There were no significant differences in genotype or allele distributions in AD, FTD or PD cases compared to controls. Neither TAU haplotype nor STH influenced CSF levels of total-tau, phospho-tau and Aβ_1–42 significantly. In AD patients with neuropathological scores of plaque and tangles, no associations with TAU haplotype and STH were found. Conclusion: We found no evidence that could support a major pathogenic role of STH and TAU haplotype in AD, FTD or PD.

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“…There have been however, several genetic studies of the tau locus in AD that have provided evidence for an association (16)(17)(18) where others have not (4,(19)(20)(21). Incorporating the STH polymorphism screening in these studies could elucidate the apparent inconsistencies in these reports and help determine whether there is an association between the tau͞STH locus and AD.…”

Section: Discussionmentioning

confidence: 99%

A polymorphic gene nested within an intron of the tau gene: Implications for Alzheimer's disease

Conrad

Vianna

Freeman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

109

124

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A previously undescribed gene, Saitohin (STH), has been discovered in the intron between exons 9 and 10 of the human tau gene. STH is an intronless gene that encodes a 128-aa protein with no clear homologs. The tissue expression of STH is similar to tau, a gene that is implicated in many neurodegenerative disorders. In humans, a single nucleotide polymorphism that results in an amino acid change (Q7R) has been identified in STH and was used in a case control study. The Q7R polymorphism appears to be over-represented in the homozygous state in late onset Alzheimer's disease subjects.

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Tau polymorphisms are not associated with Alzheimer's disease

Cited by 32 publications

References 18 publications

Candidate Gene Association Studies in Sporadic Alzheimer’s Disease

Candidate Gene Association Studies in Sporadic Alzheimer’s Disease

<i>TAU</i> Haplotype and the <i>Saitohin</i> Q7R Gene Polymorphism Do Not Influence CSF Tau in Alzheimer’s Disease and Are Not Associated with Frontotemporal Dementia or Parkinson’s Disease

A polymorphic gene nested within an intron of the tau gene: Implications for Alzheimer's disease

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