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We are analyzing https://link.springer.com/article/10.1007/s00401-012-1017-1.

Title:
The MAPT H1 haplotype is associated with tangle-predominant dementia | Acta Neuropathologica
Description:
Tangle-predominant dementia (TPD) patients exhibit cognitive decline that is clinically similar to early to moderate-stage Alzheimer disease (AD), yet autopsy reveals neurofibrillary tangles in the medial temporal lobe composed of the microtubule-associated protein tau without significant amyloid-beta (Aβ)-positive plaques. We performed a series of neuropathological, biochemical and genetic studies using autopsy brain tissue drawn from a cohort of 34 TPD, 50 AD and 56 control subjects to identify molecular and genetic signatures of this entity. Biochemical analysis demonstrates a similar tau protein isoform composition in TPD and AD, which is compatible with previous histological and ultrastructural studies. Further, biochemical analysis fails to uncover elevation of soluble Aβ in TPD frontal cortex and hippocampus compared to control subjects, demonstrating that non-plaque-associated Aβ is not a contributing factor. Unexpectedly, we also observed high levels of secretory amyloid precursor protein α (sAPPα) in the frontal cortex of some TPD patients compared to AD and control subjects, suggesting differences in APP processing. Finally, we tested whether TPD is associated with changes in the tau gene (MAPT). Haplotype analysis demonstrates a strong association between TPD and the MAPT H1 haplotype, a genomic inversion associated with some tauopathies and Parkinson disease (PD), when compared to age-matched control subjects with mild degenerative changes, i.e., successful cerebral aging. Next-generation resequencing of MAPT followed by association analysis shows an association between TPD and two polymorphisms in the MAPT 3′ untranslated region (UTR). These results support the hypothesis that haplotype-specific variation in the MAPT 3′ UTR underlies an Aβ-independent mechanism for neurodegeneration in TPD.
Website Age:
28 years and 1 months (reg. 1997-05-29).

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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Keywords {šŸ”}

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Topics {āœ’ļø}

month download article/chapter beta-amyloid precursor protein intraneuronal calcium-regulating roles nincds-adrda work group mo [nia p50-ag05681 article santa-maria maldi-tof mass spectrometry homogeneous mass-extend technology population-based linkage analyses maptƗp301s transgenic mice neurofibrillary tangle-predominant dementia alzheimer-related cortical destruction amyloid precursor protein full article pdf beta amyloid protein haplotype-based association analysis age-matched control subjects tangle predominant form 3′utr region implicated privacy choices/manage cookies significant amyloid-beta amyloid-beta quantitation moderate-stage alzheimer disease tangle-predominant dementia jellinger ka caenorhabditis elegans controls tau mrna stabilization neurofibrillary tangle type axonal targeting signal lansbury pt jr limbic neurofibrillary tangles cortical brain regions atypical protein kinase washington university school year autopsy population mild cognitive impairment appsw mice resulting abundant neurofibrillary tangles neuritic amyloid plaques microtubular protein phosphorylation abnormal tau filaments phospho-tau antisera mapt h1 haplotype h1c mapt haplotype disease neuroimaging initiative european economic area haplotype-specific variation neurobiological mechanisms involved progressive supranuclear palsy late onset families

Schema {šŸ—ŗļø}

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         headline:The MAPT H1 haplotype is associated with tangle-predominant dementia
         description:Tangle-predominant dementia (TPD) patients exhibit cognitive decline that is clinically similar to early to moderate-stage Alzheimer disease (AD), yet autopsy reveals neurofibrillary tangles in the medial temporal lobe composed of the microtubule-associated protein tau without significant amyloid-beta (Aβ)-positive plaques. We performed a series of neuropathological, biochemical and genetic studies using autopsy brain tissue drawn from a cohort of 34 TPD, 50 AD and 56 control subjects to identify molecular and genetic signatures of this entity. Biochemical analysis demonstrates a similar tau protein isoform composition in TPD and AD, which is compatible with previous histological and ultrastructural studies. Further, biochemical analysis fails to uncover elevation of soluble Aβ in TPD frontal cortex and hippocampus compared to control subjects, demonstrating that non-plaque-associated Aβ is not a contributing factor. Unexpectedly, we also observed high levels of secretory amyloid precursor protein α (sAPPα) in the frontal cortex of some TPD patients compared to AD and control subjects, suggesting differences in APP processing. Finally, we tested whether TPD is associated with changes in the tau gene (MAPT). Haplotype analysis demonstrates a strong association between TPD and the MAPT H1 haplotype, a genomic inversion associated with some tauopathies and Parkinson disease (PD), when compared to age-matched control subjects with mild degenerative changes, i.e., successful cerebral aging. Next-generation resequencing of MAPT followed by association analysis shows an association between TPD and two polymorphisms in the MAPT 3′ untranslated region (UTR). These results support the hypothesis that haplotype-specific variation in the MAPT 3′ UTR underlies an Aβ-independent mechanism for neurodegeneration in TPD.
         datePublished:2012-07-17T00:00:00Z
         dateModified:2012-07-17T00:00:00Z
         pageStart:693
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            Neurofibrillary tangle
            Tau
            Amyloid
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            3′ Untranslated region
            Aging
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            Pathology
            Neurosciences
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      headline:The MAPT H1 haplotype is associated with tangle-predominant dementia
      description:Tangle-predominant dementia (TPD) patients exhibit cognitive decline that is clinically similar to early to moderate-stage Alzheimer disease (AD), yet autopsy reveals neurofibrillary tangles in the medial temporal lobe composed of the microtubule-associated protein tau without significant amyloid-beta (Aβ)-positive plaques. We performed a series of neuropathological, biochemical and genetic studies using autopsy brain tissue drawn from a cohort of 34 TPD, 50 AD and 56 control subjects to identify molecular and genetic signatures of this entity. Biochemical analysis demonstrates a similar tau protein isoform composition in TPD and AD, which is compatible with previous histological and ultrastructural studies. Further, biochemical analysis fails to uncover elevation of soluble Aβ in TPD frontal cortex and hippocampus compared to control subjects, demonstrating that non-plaque-associated Aβ is not a contributing factor. Unexpectedly, we also observed high levels of secretory amyloid precursor protein α (sAPPα) in the frontal cortex of some TPD patients compared to AD and control subjects, suggesting differences in APP processing. Finally, we tested whether TPD is associated with changes in the tau gene (MAPT). Haplotype analysis demonstrates a strong association between TPD and the MAPT H1 haplotype, a genomic inversion associated with some tauopathies and Parkinson disease (PD), when compared to age-matched control subjects with mild degenerative changes, i.e., successful cerebral aging. Next-generation resequencing of MAPT followed by association analysis shows an association between TPD and two polymorphisms in the MAPT 3′ untranslated region (UTR). These results support the hypothesis that haplotype-specific variation in the MAPT 3′ UTR underlies an Aβ-independent mechanism for neurodegeneration in TPD.
      datePublished:2012-07-17T00:00:00Z
      dateModified:2012-07-17T00:00:00Z
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         Neurofibrillary tangle
         Tau
         Amyloid
         MAPT
         3′ Untranslated region
         Aging
         Alzheimer’s disease
         sAPPα
         Pathology
         Neurosciences
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               name:Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, USA
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            address:
               name:Department of Human Genetics, McGill University, Montreal, Canada
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               name:Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, USA
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      name:Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, USA
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      name:Division of Neuropathology, Department of Pathology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA
      name:Department of Human Genetics, McGill University, Montreal, Canada
      name:Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, USA
      name:Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, USA
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