White matter tauopathy with globular glial inclusions: a distinct sporadic frontotemporal lobar degeneration.
Frontotemporal lobar degenerations are a group of disorders characterized by circumscribed degeneration of the frontal and temporal lobes and diverse histopathologic features. We report clinical, neuropathologic, ultrastructural, biochemical, and genetic data on 7 individuals with a 4-repeat tauopathy characterized by the presence of globular glial inclusions (GGIs) in brain white matter. Clinical manifestations were compatible with the behavioral variant of frontotemporal dementia and included motor neuron symptoms; there was prominent neuronal loss in the frontal and temporal cortex, subiculum, and amygdala. The surrounding white matter showed abundant GGIs composed of abnormal filaments present mostly in oligodendrocytes. The severity of white matter tau abnormalities correlated with a reduction in myelin and axons and with microglial activation. Western blotting of sarkosyl-insoluble tau demonstrated the presence of 2 major tau bands of 64 and 68 kd. No mutations in the microtubule-associated protein tau gene were detected in 2 affected individuals. We propose that 4-repeat tau-immunoreactive GGIs are the neuropathologic hallmark of a distinct sporadic tauopathy with variable clinical presentations that include frontotemporal dementia and occasionally upper motor neuron disease. This type of tauopathy with GGIs expands the group of neurodegenerativedisorders in which oligodendroglial pathology predominates, beyond the synucleinopathy multiple system atrophy disorders.
Kovacs
Gabor G
GG
Institute of Neurology, Medical University of Vienna, Vienna, Austria. gabor.kovacs@meduniwien.ac.at
Majtenyi
Katalin
K
Spina
Salvatore
S
Murrell
Jill R
JR
Gelpi
Ellen
E
Hoftberger
Romana
R
Fraser
Graham
G
Crowther
R Anthony
RA
Goedert
Michel
M
Budka
Herbert
H
Ghetti
Bernardino
B
D000368:Aged; D001921:Brain / Q000473:pathology*; D003704:Dementia / Q000235:genetics / Q000473:pathology*; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000235:genetics / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009457:Neuroglia / Q000473:pathology*; D016612:Paraffin Embedding; D024801:Tauopathies / Q000235:genetics / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D016875:tau Proteins; D005557:Formaldehyde
Acta Neuropathol. 1999 Apr;97(4):423-8
10208284
Neuropathol Appl Neurobiol. 2008 Aug;34(4):468-72
18208485
Nat Genet. 2005 Aug;37(8):806-8
16041373
J Neuropathol Exp Neurol. 2005 Oct;64(10):839-46
16215455
Alzheimer Dis Assoc Disord. 2005 Oct-Dec;19 Suppl 1:S3-6
16317256
Acta Neuropathol. 2005 Dec;110(6):600-9
16328530
Acta Neuropathol. 2006 Apr;111(4):329-40
16552612
J Neuropathol Exp Neurol. 2006 Apr;65(4):396-405
16691120
Nature. 2006 Aug 24;442(7105):920-4
16862115
Nature. 2006 Aug 24;442(7105):916-9
16862116
Acta Neuropathol. 2006 Sep;112(3):341-8
16804710
Acta Neuropathol. 2006 Oct;112(4):389-404
16906426
Science. 2006 Oct 6;314(5796):130-3
17023659
J Struct Biol. 2000 Jun;130(2-3):271-9
10940231
J Neurol Sci. 2000 Oct 1;179(S 1-2):50-8
11054485
J Neuropathol Exp Neurol. 2001 Apr;60(4):328-41
11305868
Nat Rev Neurosci. 2001 Jul;2(7):492-501
11433374
Annu Rev Neurosci. 2001;24:1121-59
11520930
Neurochem Int. 2001 Nov-Dec;39(5-6):469-79
11578782
Ann Neurol. 2001 Oct;50(4):494-502
11601500
Acta Neuropathol. 2002 Feb;103(2):115-8
11810176
J Neurol Sci. 2002 Mar 30;195(2):123-7
11897242
Neurosci Lett. 2002 Sep 13;330(1):84-8
12213640
Acta Neuropathol. 2003 Aug;106(2):181-7
12783250
Acta Neuropathol. 2003 Nov;106(5):419-35
12955398
Nat Genet. 2004 Apr;36(4):377-81
15034582
J Neurol Sci. 1989 Dec;94(1-3):79-100
2559165
J Lipid Res. 1990 Mar;31(3):545-8
2341813
Neurosci Lett. 1990 Dec 11;120(2):163-6
2293103
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2288-92
1706519
Neurology. 1991 Apr;41(4):479-86
2011243
Science. 1991 Oct 4;254(5028):97-9
1925564
Neuron. 1992 Jan;8(1):159-68
1530909
Mov Disord. 1994 Mar;9(2):161-6
8196676
Ann Neurol. 1997 Feb;41(2):277-81
9029080
Ann Neurol. 1998 Jun;43(6):815-25
9629852
Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7737-41
9636220
Nature. 1998 Jun 18;393(6686):702-5
9641683
Eur Neurol. 1998 Aug;40(2):71-7
9693235
Neurosci Lett. 1998 Jul 31;251(3):205-8
9726379
Neurology. 1998 Dec;51(6):1546-54
9855500
J Neuropathol Exp Neurol. 1998 Dec;57(12):1099-111
9862632
Hum Mol Genet. 1999 Apr;8(4):711-5
10072441
Science. 2006 Nov 3;314(5800):777-81
17082447
Biochem Biophys Res Commun. 2006 Dec 22;351(3):602-11
17084815
Curr Opin Neurol. 2006 Dec;19(6):565-71
17102695
Brain Pathol. 2007 Jan;17(1):74-82
17493041
Acta Neuropathol. 2007 Jul;114(1):5-22
17579875
Science. 2008 Mar 21;319(5870):1668-72
18309045
Nat Genet. 2008 May;40(5):572-4
18372902
Ann Neurol. 2008 Apr;63(4):535-8
18288693
Acta Neuropathol. 2005 Mar;109(3):329-38
15841415