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neurofibrillary tangle (NFT)

Large, non membrane-bound bundles of abnormal fibers occupying much of the perinuclear cytoplasm. see figure Etiology: NFT are seen in neurons of patients with various disorders, including: 1) aging* 2) Alzheimer's disease* 3) Down's syndrome* 4) Parkinson-dementia complex of Guam 5) postencephalitic parkinsonism 6) dementia pugilistica 7) Hallervorden-Spatz disease 8) progressive supranuclear palsy 9) subacute sclerosing panencephalitis [SSPE] 10) adult neuronal ceroid lipofuscinosis (Kufs' disease) 11) familial British dementia * Neuritic plaques are also observed in these disorders. Structure: - in Alzheimer's disease, the NFTs consist largely of paired helical filaments (PHF) - some tangle-bearing neurons also contain straight filaments, 10-15 nm filaments in diameter - components of NFT: a) microtubule associated protein tau (hyperphosphorylated) 1] may be truncated of its C-terminal 20 amino acid residues 2] proteolysis by one of several caspases at Asp421 is implicated [4] b) ubiquitin, UCHL1, UBQLN1 c) neurofilament d) neural thread protein e) apolipoprotein E f) heme oxygenase-1 g) NF kappa B p50 h) Big SAAS or Little SAAS i) phosphorylated DPYSL2 Pathology: - caspase activity may be essential for formation of NFT - nitration of tau is found in association with NFT [5]

Related

disorders with neurofibrillary tangles paired helical filament (PHF) straight filament

General

abnormal morphologic structure (malformation)

References

  1. Smith MA, Kutty RK, Richey PL, Yan SD, Stern D, Chader GJ, Wiggert B, Petersen RB, Perry G. Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. Am J Pathol. 1994 Jul;145(1):42-7. PMID: 8030754 [Heme Oxygenase-1]
  2. Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, Slattery T, Zhao L, Nagashima M, Morser J, Migheli A, Nawroth P, Stern D, Schmidt AM. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature. 1996 Aug 22;382(6593):685-91. PMID: 8751438 [NF kappa B p50]
  3. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: 11274343
  4. Gamblin TC et al, Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. Proc Natl Acad Sci U S A. Aug 19;100(17):10032-7. 2003 PMID: 12888622
  5. Horiguchi T et al, Nitration of tau protein is linked to neurodegeneration in tauopathies. Am J Pathol. 2003 Sep;163(3):1021-31. Erratum in: Am J Pathol. 2003 Dec;163(6):2645. PMID: 12937143

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