title: TDP-43 variants of frontotemporal lobar degeneration.
abstract: It has been only 5 years since the identification of TDP-43 as the major protein component of the ubiquitinated inclusions in FTLD-U. At that time, there were approximately a dozen papers about TDP-43; today, a "TDP-43" search reveals almost 600 papers. It is now clear that the majority of FTLD cases containing tau- and alpha-synuclein-negative, ubiquitin-positive inclusions (FTLD-U) are FTLD-TDP. The spectrum of TDP-43 proteinopathies includes FTLD-TDP with or without ALS, with or without mutations in GRN, VCP, or TARDBP, with or without chromosome 9p linkage, and sporadic and non-SOD1 familial ALS with or without FTLD-TDP. There are four sub-types of FTLD-TDP, and these correlate with specific clinical and genetic profiles. Sub-types are determined by the presence, predominance, and distribution of the various TDP-43 immunopositive insoluble aggregates-neuronal cytoplasmic inclusions, neuronal intranuclear inclusions, and dystrophic neurites. In this paper, FTLD-TDP pathologic sub-types will be described, and examples of each sub-type will be shown, and implications for future research will be discussed.
authors: Department of Pathology and Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. e-bigio@northwestern.edu
authors: Eileen H
authors: EH
authors: Bigio
references: Ann Neurol. 2008 Jul;64(1):60-70
references: 18546284
references: Acta Neuropathol. 2009 Sep;118(3):349-58
references: 19455346
references: Am J Pathol. 2007 Jul;171(1):227-40
references: 17591968
references: Acta Neuropathol. 2004 Sep;108(3):207-12
references: 15170577
references: Neurology. 2004 Aug 10;63(3):538-42
references: 15304590
references: Ann Neurol. 2007 May;61(5):435-45
references: 17469117
references: Acta Neuropathol. 2008 Jan;115(1):123-31
references: 18004574
references: Acta Neuropathol. 2007 Jul;114(1):5-22
references: 17579875
references: Acta Neuropathol. 2007 Jul;114(1):63-70
references: 17492294
references: Acta Neuropathol. 2006 Nov;112(5):539-49
references: 17021754
references: Acta Neuropathol. 2007 May;113(5):521-33
references: 17219193
references: Nature. 2006 Aug 24;442(7105):920-4
references: 16862115
references: J Neuropathol Exp Neurol. 2006 Jun;65(6):571-81
references: 16783167
references: Acta Neuropathol. 2009 Feb;117(2):137-49
references: 19125255
references: Am J Pathol. 2008 Jul;173(1):182-94
references: 18535185
references: Acta Neuropathol. 2009 Nov;118(5):633-45
references: 19618195
references: J Neuropathol Exp Neurol. 2008 Apr;67(4):271-9
references: 18379440
references: J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):196-203
references: 20562461
references: Brain. 2008 May;131(Pt 5):1282-93
references: 18362096
references: J Neurochem. 2008 May;105(3):797-806
references: 18088371
references: Biochem Biophys Res Commun. 2006 Dec 22;351(3):602-11
references: 17084815
references: J Virol. 1995 Jun;69(6):3584-96
references: 7745706
references: Am J Pathol. 2006 Oct;169(4):1343-52
references: 17003490
references: J Neural Transm (Vienna). 2010 Feb;117(2):227-39
references: 20012109
references: Brain. 2009 Nov;132(Pt 11):2922-31
references: 19674978
references: Acta Neuropathol. 2007 Jul;114(1):55-61
references: 17457594
references: Rejuvenation Res. 2010 Oct;13(5):509-17
references: 20645878
references: Brain. 2010 Jun;133(Pt 6):1763-71
references: 20472655
references: Nature. 2006 Aug 24;442(7105):916-9
references: 16862116
references: Acta Neuropathol. 2010 Jan;119(1):1-4
references: 19924424
references: Acta Neuropathol. 2007 Oct;114(4):335-45
references: 17639426
references: Acta Neuropathol. 2008 Aug;116(2):147-57
references: 18536926
references: Neurology. 2009 May 12;72(19):1669-76
references: 19433740
references: Neurology. 2007 Sep 11;69(11):1113-21
references: 17522386
references: Ann Neurol. 2007 May;61(5):427-34
references: 17469116
references: Hum Mutat. 2009 Nov;30(11):E974-83
references: 19655382
references: BMC Neurol. 2008 Aug 29;8:32
references: 18755042
references: Science. 2006 Oct 6;314(5796):130-3
references: 17023659