Tangle evolution linked to differential 3- and 4-repeat tau isoform deposition: a double immunofluorolabeling study using two monoclonal antibodies.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Author(s): Uchihara T;Uchihara T; Hara M; Nakamura A; Hirokawa K
  • Source:
    Histochemistry and cell biology [Histochem Cell Biol] 2012 Feb; Vol. 137 (2), pp. 261-7. Date of Electronic Publication: 2011 Nov 25.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: Germany NLM ID: 9506663 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-119X (Electronic) Linking ISSN: 09486143 NLM ISO Abbreviation: Histochem Cell Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin : Springer,
    • Subject Terms:
      Alzheimer Disease/*metabolism ; Neurodegenerative Diseases/*metabolism ; Neurofibrillary Tangles/*metabolism ; Supranuclear Palsy, Progressive/*metabolism ; tau Proteins/*metabolism; Aged ; Aged, 80 and over ; Alzheimer Disease/pathology ; Antibodies, Monoclonal ; Humans ; Immunohistochemistry ; Neurodegenerative Diseases/pathology ; Protein Isoforms/metabolism ; Staining and Labeling ; Supranuclear Palsy, Progressive/pathology
    • Abstract:
      Double immunofluorolabeling for 3-repeat (3R) and 4-repeat (4R) tau was performed with two monoclonal antibodies, RD3 and RD4, after an additional pretreatment with potassium permanganate and oxalic acid to eliminate nonspecific 3R tau cytoplasmic staining. This method involves hyperdilution of one of the primary monoclonal antibodies (≥100-fold), making it undetectable by usual secondary antibodies. The hyperdiluted primary antibody can then only be detected after tyramide amplification. Subsequent application of the other monoclonal antibody at its usual concentration allows double immunofluorolabeling without cross-reaction. This novel method revealed that tau immunoreactivity (IR) in the hippocampal pyramidal neurons of Alzheimer's disease (AD) brains is heterogeneous in that pretangle neurons exhibit 4R-selective (3R-/4R+) IR, ghost tangles exhibit 3R-selective (3R+/4R-) IR, and neurofibrillary tangles exhibit both 3R and 4R (3R+/4R+) IR. Some nigral neurons exhibited RD3 IR in both AD and corticobasal degeneration/progressive supranuclear palsy (CBD/PSP) brains. However, in CBD/PSP cases, 3R IR was always superimposed on 4R IR, while 3R-selective neurons were present in AD cases. These differential isoform profiles may provide a pivotal molecular reference, closely related to the morphological evolution of tau-positive neurons, which may be variable according to disease (CBD/PSP vs. AD), lesion site (cerebral cortex and substantia nigra), or the stage of evolution (from pretangles to ghost tangles). These findings should provide a more comprehensive understanding of the histological differentiation of various tau deposits in human neurodegenerative disease.
    • References:
      Neuropathology. 2006 Oct;26(5):457-70. (PMID: 17080726)
      J Neurol Sci. 1998 Jul 15;159(1):73-81. (PMID: 9700707)
      J Biol Chem. 2010 Nov 26;285(48):37920-6. (PMID: 20921227)
      Acta Neuropathol. 2001 Jun;101(6):535-9. (PMID: 11515780)
      Biochemistry. 2011 May 24;50(20):4330-6. (PMID: 21510682)
      J Biol Chem. 2010 Nov 5;285(45):34885-98. (PMID: 20805224)
      Acta Neuropathol. 1999 Jun;97(6):565-76. (PMID: 10378375)
      Brain Res. 1989 Jan 16;477(1-2):90-9. (PMID: 2495152)
      FEBS Lett. 2002 Nov 20;531(3):538-42. (PMID: 12435607)
      Brain. 2009 May;132(Pt 5):1324-34. (PMID: 19321462)
      J Histochem Cytochem. 2003 Sep;51(9):1201-6. (PMID: 12923245)
      PLoS One. 2010 May 25;5(5):e10810. (PMID: 20520830)
      Brain Pathol. 2012 Jan;22(1):67-78. (PMID: 21672073)
      Handb Clin Neurol. 2008;89:161-72. (PMID: 18631741)
      Neurology. 1994 Nov;44(11):2015-9. (PMID: 7969952)
      J Neurosci Methods. 2004 May 30;135(1-2):67-70. (PMID: 15020090)
      Acta Neuropathol. 2001 Sep;102(3):285-92. (PMID: 11585254)
      Brain Pathol. 2011 Mar;21(2):180-8. (PMID: 20825412)
      Neuropathology. 2006 Feb;26(1):50-6. (PMID: 16521479)
      Acta Neuropathol. 2007 Feb;113(2):107-17. (PMID: 17089134)
      Acta Neuropathol. 1991;81(6):591-6. (PMID: 1831952)
      J Neuropathol Exp Neurol. 2002 Nov;61(11):935-46. (PMID: 12430710)
      Neuropathol Appl Neurobiol. 2003 Jun;29(3):288-302. (PMID: 12787326)
      Handb Clin Neurol. 2008;89:415-30. (PMID: 18631764)
      J Alzheimers Dis. 2008 May;14(1):1-16. (PMID: 18525123)
      J Histochem Cytochem. 1996 Dec;44(12):1353-62. (PMID: 8985127)
      Acta Neurol Scand. 2005 Nov;112(5):327-34. (PMID: 16218916)
      Histochem Cell Biol. 2000 Dec;114(6):447-51. (PMID: 11201605)
      Neurosci Lett. 2006 Sep 11;405(1-2):29-33. (PMID: 16859829)
      J Neuropathol Exp Neurol. 1996 Jan;55(1):97-105. (PMID: 8558176)
    • Accession Number:
      0 (Antibodies, Monoclonal)
      0 (Protein Isoforms)
      0 (tau Proteins)
    • Publication Date:
      Date Created: 20111126 Date Completed: 20120705 Latest Revision: 20211021
    • Publication Date:
      20240829
    • Accession Number:
      10.1007/s00418-011-0891-2
    • Accession Number:
      22116524