Specific detection of pathological three-repeat tau after pretreatment with potassium permanganate and oxalic acid in PSP/CBD brains.
Immunohistochemisty with RD3, a monoclonal antibody specific for three-repeat (3R) tau, is sometimes hampered by diffuse neuronal staining on formalin-fixed, paraffin-embedded sections pretreated with formic acid and heating. Additional pretreatment with potassium permanganate followed by oxalic acid completely eliminated this diffuse RD3-immunoreactivity (IR) in neurons. Furthermore, this additional pretreatment uniformly enhanced RD3-IR, as well as RD4-IR, a monoclonal antibody specific for four-repeat (4R) tau, on pathological deposits with tau IR. This enhanced sensitivity and specificity may allow more reliable identification of 3R and 4R tau in pathological deposits, which may be variable dependent on disease and regions. Cerebral cortex and midbrain from 8 patients [5 progressive supranuclear palsy (PSP) and 3 corticobasal degeneration (CBD)] were screened for RD3- and RD4-IR with this improved procedure. In addition to RD4-positive structures found both in cerebral cortex and brainstem, RD3-positive neurofibrillary tangles (NFTs) were also found in midbrain in 7 of these 8 cases but not in the cortex. Multi-labeling study demonstrated that most of RD3-negative neurons were positive for RD4. This reliable demonstration of pathological 3R tau deposits in the brainstem of PSP/CBD, so far presumably characterized by deposition of 4R tau, is useful to map tau-positive lesions according to their biochemical composition.
Uchihara
Toshiki
T
Department of Neurology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan. uchihara-ts@igakuken.or.jp
Nakamura
Ayako
A
Shibuya
Katsuhiko
K
Yagishita
Saburo
S
D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007202:Indicators and Reagents; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019815:Oxalic Acid; D011196:Potassium Permanganate; D012680:Sensitivity and Specificity; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000032:analysis*
D000911:Antibodies, Monoclonal; D007202:Indicators and Reagents; D016875:tau Proteins; D011196:Potassium Permanganate; D019815:Oxalic Acid
J Neuropathol Exp Neurol. 2010 Jan;69(1):40-52
20010304
Acta Neuropathol. 2007 May;113(5):483-99
17401570
Brain. 2005 Jun;128(Pt 6):1247-58
15788542
Neurology. 1994 Nov;44(11):2015-9
7969952
J Histochem Cytochem. 1957 Jul;5(4):346-53
13463308
J Neuropathol Exp Neurol. 2009 Sep;68(9):1029-36
19680140
Brain Res Mol Brain Res. 2004 Feb 5;121(1-2):95-101
14969740
Acta Neuropathol. 2006 Oct;112(4):389-404
16906426
FEBS Lett. 2002 Nov 20;531(3):538-42
12435607
J Neuropathol Exp Neurol. 2002 Dec;61(12):1040-7
12484566
Acta Neuropathol. 1992;84(3):265-72
1384266
Neuropathol Appl Neurobiol. 2009 Dec;35(6):532-54
19682326
J Neuropathol Exp Neurol. 1996 Jan;55(1):97-105
8558176
Acta Neuropathol. 1994;88(4):379-83
7839832
Neuropathology. 2006 Oct;26(5):457-70
17080726
Acta Neuropathol. 2004 Feb;107(2):181-2
14652684
J Neurol. 1995 Aug;242(8):485-9
8530974
Acta Neuropathol. 2006 Apr;111(4):329-40
16552612
Neuropathol Appl Neurobiol. 2003 Jun;29(3):288-302
12787326