The H1c haplotype at the MAPT locus is associated with Alzheimer's disease

Myers, Amanda; Kaleem, Mona; Marlowe, Lauren; Pittman, Alan; Lees, Andrew J.; Fung, Hon Chung; Duckworth, Jaime; Leung, Doris G.; Gibson, A. H.; Morris, Christopher M.; Silva, R. de; Hardy, John

doi:10.1093/hmg/ddi241

Cited by 202 publications

(204 citation statements)

References 20 publications

(16 reference statements)

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“…Mutations have been found in MAPT in the familial form of FTDP-17 (26). Similarly, a common polymorphism has been reported in MAPT to be strongly associated with progressive supranuclear palsy, corticobasal degeneration, and AD (27)(28)(29)(30).…”

mentioning

confidence: 73%

Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro

Qureshi¹,

Paudel

2011

Journal of Biological Chemistry

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mentioning

confidence: 73%

Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro

Qureshi¹,

Paudel

2011

Journal of Biological Chemistry

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“…The Zurich case-control series, the Newcastle Brain Bank (U.K. series), and various brain banks throughout the United States (U.S. series) have been recently described (23,24). The affected sibling pairs (ASPs) sample was provided by the National Institute of Mental Health (NIMH), the National Cell Repository for AD (Grant U24 AG21886) and the United Kingdom.…”

Section: Methodsmentioning

confidence: 99%

“…Upon genotyping, 398 Caucasian cases and 339 age-and ethnicitymatched controls coming from the Zurich series (23), the Newcastle Brain Bank (U.K. series) (24), and various brain banks throughout the United States (U.S. series) (24) (see Methods), we noted a trend toward association in single-locus tests for 14e (P ϭ 0.075, Table 1) and significant association for 18e with AD (P ϭ 0.037, Table 1) in the combined multicenter sample (Zurich/U.K./U.S. series).…”

Section: Genetic Variation In Lrp6 Ismentioning

confidence: 99%

Common genetic variation within the Low-Density Lipoprotein Receptor-Related Protein 6 and late-onset Alzheimer's disease

Ferrari

Papassotiropoulos

Biechele

et al. 2007

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

258

224

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Genome-wide linkage studies have defined a broad susceptibility region for late-onset Alzheimer's disease on chromosome 12, which contains the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) gene, a coreceptor for Wnt signaling. Here, we report the association between common LRP6 variants and late-onset Alzheimer's disease in a multicenter case-control series as well as in a large family-based series ascertained by the National Institute of Mental Health-National Institute on Aging Genetics Initiative. As shown in the genome-wide linkage studies, our association depends mainly on apolipoprotein E-4 (APOE-4) carrier status. Haplotype tagging single-nucleotide polymorphisms (SNPs) with a set of seven allelic variants of LRP6 identified a putative risk haplotype, which includes a highly conserved coding sequence SNP: Ile-1062 3 Val. Functional analyses revealed that the associated allele Val-1062, an allele previously linked to low bone mass, has decreased ␤-catenin signaling in HEK293T cells. Our study unveils a genetic relationship between LRP6 and APOE and supports the hypothesis that altered Wnt/␤-catenin signaling may be involved in this neurodegenerative disease.neurodegenerative ͉ LRP-6 ͉ single-nucleotide polymorphism ͉ APOE ͉ Wnt

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“…Hyplotype H1c carrying SNP rs242557 G to A substitution at the MAPT locus was shown to be associated with the risk of Alzheimer's disease. 6 Therefore, the analyte binding arms of the probe were tailored to recognize the major allele rs242557-G ( Figure 1B,C). Figure 2 demonstrates the change of light absorption of the solution containing binary DNA peroxidase probe when 3-3′-diaminobenzidine tetrahydrochloride (DAB) was used as an oxidizable substrate.…”

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confidence: 99%

Split DNA Enzyme for Visual Single Nucleotide Polymorphism Typing

2008

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Single nucleotide polymorphisms (SNPs) are the most abundant forms of genetic variations in the human genome. Large-scale sequence analysis is needed for a population-based genetic risk assessment and diagnostic tests once a mutation has been identified. However, most of the methods for SNP screening require enzymatic manipulations such as endonuclease digestion, ligation or primer extension, and often separation of the resultant products. 1 These labor intensive and time-consuming procedures are some of the biggest impediments to moving SNP typing techniques to point-of-care settings, which require straightforward, inexpensive, and disposable detection formats. Toward the fulfilling of these requirements a probe for visual SNP detection was developed in this study.Binary probes for fluorimetric analysis of single nucleotide substitutions were developed earlier. 2 The probes demonstrate improved selectivity in comparison with conventional hybridization-based approaches, since the two parts of the probes form relatively short (7-10 nucleotide) duplexes with target sequences. These short hybrids are extremely sensitive to single nucleotide substitutions at room temperature and generate a high fluorescent signal only in the presence of the fully complementary targets. Binary probes do not require precise temperature control for SNP typing. 2d,e However, a fluorimeter is required for signal registration. To avoid the need for instruments for both SNP typing and signal readout, a binary probe that generates a visual output after hybridization to the target was designed in this study based on a peroxidase-like DNA enzyme.A hemin binding DNA aptamer ( Figure 1A) was obtained earlier by in vitro selection. 3 It was shown that in the presence of hemin it forms a guanine quartet, which demonstrates hydrogen peroxidase-like activity ~250 times greater than hemin alone. 4 This DNA enzyme was used for the design of allosterically regulated sensors for nucleic acids, AMP, and lysozyme that allow colorimetric or luminescent readouts. 5 To construct a binary probe, the sequence of the peroxidase-like DNA enzyme ( Figure 1A) was split into two halves, the deoxycytidine was removed, and the analyte binding arms were added to each half via triethylene glycol linkers ( Figure 1B). In the absence of nucleic acid analyte strands α and β exist predominantly in the dissociated form (at certain concentrations and buffer conditions), while assembling in a Gquadruplex structure and acquiring peroxidase activity when hybridized to the adjacent positions of the analyte ( Figure 1C). The active peroxidase catalyzes the oxidation of a colorless substrate to a colored product, which can be detected both visually and spectrophotometrically. DNA that is a part of the coding sequence for microtubule associated protein tau (MAPT) was chosen as a model analyte for this study. Hyplotype H1c carrying SNP rs242557 G to A

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The H1c haplotype at the MAPT locus is associated with Alzheimer's disease

Cited by 202 publications

References 20 publications

Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro

Parkinsonian Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and α-Synuclein Mutations Promote Tau Protein Phosphorylation at Ser262 and Destabilize Microtubule Cytoskeleton in Vitro

Common genetic variation within the Low-Density Lipoprotein Receptor-Related Protein 6 and late-onset Alzheimer's disease

Split DNA Enzyme for Visual Single Nucleotide Polymorphism Typing

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