Comparative Biochemistry of Tau in Progressive Supranuclear Palsy, Corticobasal Degeneration, FTDP‐17 and Pick's Disease

  title={Comparative Biochemistry of Tau in Progressive Supranuclear Palsy, Corticobasal Degeneration, FTDP‐17 and Pick's Disease},
  author={Luc Bu{\'e}e and André Delacourte},
  journal={Brain Pathology},
Neurodegenerative disorders referred to as tauopathies have cellular hyperphosphorylated tau protein aggregates in the absence of amyloid deposits. Comparative biochemistry of tau aggregates shows that they differ in both phosphorylation and content of tau isoforms. The six tau isoforms found in human brain contain either three (3R) or four microtubule‐binding domains (4R). In Alzheimer's disease, all six tau isoforms are abnormally phosphorylated and aggregate into paired helical filaments… 
Pathological Tau Phenotypes: The Weight of Mutations, Polymorphisms, and Differential Neuronal Vulnerabilities
Stably transfected human neuroblastoma SY5Y cell lines with either 3R‐ or 4R‐tau isoforms are established and cell morphology and tau phosphorylation were modified, suggesting that cells undergo profound changes in their metabolism and viability.
Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy
The H1 haplotype does not have a major influence on the pathological or biochemical phenotype of PSP and had no effect on the 4R to 3R ratio or on tau and amyloid burdens.
Structural Polymorphism in Tau Filaments: An Implication for Neurodegenerative Diseases
In vitro experiments show that the seeded filament growth, a prerequisite for tau spreading in tissue culture and brain, is crucially dependent on the isoform composit ion of individual seeds.
Cellular tau pathology and immunohistochemical study of tau isoforms in sporadic tauopathies
  • Mari Yoshida
  • Biology
    Neuropathology : official journal of the Japanese Society of Neuropathology
  • 2006
The immunohistochemistry of tau isoforms in autopsied brains showed heterogeneity in PiD, and was not uniform in the basal ganglia and brain stem in PSP and CBD, which suggested that the isoform composition of sporadic tauopathies may have a spectrum in individual cases.
Neuropathology of Frontotemporal Lobar Degeneration-Tau (FTLD-Tau)
The anatomical distribution of tau pathology determines the clinical presentation of PSP and CBD, as well as PiD, and the basis for this selective cortical vulnerability in FTLD-tau is unknown.
Glial and neuronal tau pathology in tauopathies: characterization of disease-specific phenotypes and tau pathology progression.
Tau pathology in glial cells largely parallels, but is not identical to, that in neurons in many tauopathies, and disease-specific astroglial phenotypes depend on the primary amino acid sequence of tau.
Human Tau Isoforms and Proteolysis for Production of Toxic Tau Fragments in Neurodegeneration
This assessment identifies the gap in the field on understanding the details of proteolytic steps used to convert each tau isoform into fragments and can lead to new protease targeted drug strategies to prevent the formation of toxic tau fragments in tauopathy neurodegenerative diseases.
Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule‐binding repeat domains as demonstrated by new specific monoclonal antibodies
Two monoclonal antibodies, RD3 and RD4, are developed that effectively distinguish these closely related tau isoforms that are useful tools for analysing t Tau isoform expression and distribution as well as pathological changes in the human brain.
Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains
Examination of tau mRNA and protein levels in frontal cortex from 15 sporadic FTLD, 21 PSP, 5 CBD, 15 Alzheimer’s disease (AD) and 16 control brains demonstrated increased but largely variable 4R tau/3R t Tau mRNA ratios, suggesting heterogeneous pathophysiological processes within these disorders.


Neurofibrillary Degeneration in Progressive Supranuclear Palsy and Corticobasal Degeneration
A third group of neurodegenerative disorders characterized by intraneuronal inclusions exclusively constituted of tau isoforms containing the sequence corresponding to exon 10, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).
Hyperphosphorylated tau proteins differentiate corticobasal degeneration and Pick’s disease
Since there is a great diversity of neurodegenerative disorders with substantial clinical and neuropathological overlap, the electrophoretic profile of tau proteins could represent a useful marker for the type of Neurodegeneration.
Specific Pathological Tau Protein Variants Characterize Pick's Disease
The 55 and 64 kDa Tau doublet appears to be specific to PiD, less acidic than AD Tau proteins, and well correlated with the presence of PB.
Neurofibrillary degeneration in amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. Immunochemical characterization of tau proteins.
The data suggest that the tau triplet found in amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam is similar to that observed in Alzheimer's disease, and the regional distribution of tau proteins differs in these disorders.
Fibrillogenesis of Tau: Insights from Tau Missense Mutations in FTDP‐17
Findings suggest involvement of at least two mechanisms in the pathogenesis of FTDP‐17, particularly in the 5'splice site of exon 10 and in exons 9–13 of the tau gene.
Tau‐positive dial Inclusions in Progressive Supranuclear Palsy, Corticobasal Degeneration and Pick's Disease
These distinctive glial lesions most likely reflect fundamental alterations in isoform composition of tau as well as its specific cellular and regional expression in sporadic tauopathies.
Neurofibrillary Tangles in Progressive Supranuclear Palsy Contain the Same Tau Epitopes Identified in Alzheimer's Disease PHFtau
Despite differences in the distribution, ultrastructure and immunoblot profile of NFTs in PSP and AD, the same constellation of tau epitopes is present in the abnormal tau proteins in PSP (PSPtau) and AD N FTs.
Mutation in the tau gene in familial multiple system tauopathy with presenile dementia.
The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene, which has major implications for Alzheimer's disease and other tauopathies.