title: TDP-43 frontotemporal lobar degeneration and autoimmune disease.
abstract: BACKGROUND
  The aetiology and pathogenesis of non-genetic forms of frontotemporal dementia (FTD) is unknown and even with the genetic forms of FTD, pathogenesis remains elusive. Given the association between systemic inflammation and other neurodegenerative processes, links between autoimmunity and FTD need to be explored.
  
  
  OBJECTIVE
  To describe the prevalence of systemic autoimmune disease in semantic variant primary progressive aphasia (svPPA), a clinical cohort, and in progranulin (PGRN) mutation carriers compared with neurologically healthy normal controls (NC) and Alzheimer's disease (AD) as dementia controls.
  
  
  METHODS
  Case control.
  
  
  METHODS
  Academic medical centres.
  
  
  METHODS
  129 svPPA, 39 PGRN, 186 NC and 158 AD patients underwent chart review for autoimmune conditions. A large subset of svPPA, PGRN and NC cohorts underwent serum analysis for tumour necrosis factor α (TNF-α) levels.
  
  
  METHODS
  χ(2) Comparison of autoimmune prevalence and follow-up logistic regression.
  
  
  RESULTS
  There was a significantly increased risk of autoimmune disorders clustered around inflammatory arthritides, cutaneous disorders and gastrointestinal conditions in the svPPA and PGRN cohorts. Elevated TNF-α levels were observed in svPPA and PGRN compared with NC.
  
  
  CONCLUSIONS
  svPPA and PGRN are associated with increased prevalence of specific and related autoimmune diseases compared with NC and AD. These findings suggest a unique pattern of systemic inflammation in svPPA and PGRN and open new research avenues for understanding and treating disorders associated with underlying transactive response DNA-binding protein 43 aggregation.
authors.affiliation: UCSF Memory and Aging Center, University of California San Francisco, San Francisco, California 94143-1207, USA. zmiller@memory.ucsf.edu
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Miller
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Rankin
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Leonel T
authors.initials: LT
authors.lastname: Takada
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Sturm
authors.forename: Clare M
authors.initials: CM
authors.lastname: Cleveland
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Jaeger
authors.forename: Trisha
authors.initials: T
authors.lastname: Stan
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Heggeli
authors.forename: Sandy Chan
authors.initials: SC
authors.lastname: Hsu
authors.forename: Anna
authors.initials: A
authors.lastname: Karydas
authors.forename: Baber K
authors.initials: BK
authors.lastname: Khan
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology; D018888:Aphasia, Primary Progressive / Q000473:pathology; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000473:pathology* / Q000523:psychology; D015331:Cohort Studies; D004522:Educational Status; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000453:epidemiology / Q000473:pathology* / Q000523:psychology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009483:Neuropsychological Tests; D015995:Prevalence; D000077153:Progranulins; D011569:Psychiatric Status Rating Scales; D057177:TDP-43 Proteinopathies / Q000453:epidemiology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D014409:Tumor Necrosis Factor-alpha
keywords: DEMENTIA; EPIDEMIOLOGY; IMMUNOLOGY; RHEUMATOLOGY
references.citation: N Engl J Med. 2002 Jan 17;346(3):180-8
references.pmid: 11796853
references.citation: Neurology. 2009 Nov 3;73(18):1462-8
references.pmid: 19776374
references.citation: J Autoimmun. 2013 May;42:29-38
references.pmid: 23149338
references.citation: Brain. 2010 Jan;133(Pt 1):300-6
references.pmid: 19805492
references.citation: Gut. 2007 Apr;56(4):504-8
references.pmid: 17135309
references.citation: Arch Dermatol. 2005 Dec;141(12):1537-41
references.pmid: 16365254
references.citation: Mayo Clin Proc. 2001 Jun;76(6):593-9
references.pmid: 11393497
references.citation: Arthritis Rheum. 2008 Jan;58(1):15-25
references.pmid: 18163481
references.citation: Acta Neuropathol. 2007 Jul;114(1):31-8
references.pmid: 17569065
references.citation: Autoimmunity. 2005 Jun;38(4):303-17
references.pmid: 16206513
references.citation: J Neurol Neurosurg Psychiatry. 2003 Nov;74(11):1574-6
references.pmid: 14617722
references.citation: Arch Neurol. 1994 Dec;51(12):1198-204
references.pmid: 7986174
references.citation: Curr Opin Rheumatol. 2009 Jan;21(1):62-70
references.pmid: 19093325
references.citation: Neurology. 2005 Dec 13;65(11):1817-9
references.pmid: 16344531
references.citation: Arch Dermatol. 1977 Jan;113(1):47-52
references.pmid: 831622
references.citation: J Pathol. 2001 Aug;194(4):398-405
references.pmid: 11523046
references.citation: J Autoimmun. 2009 Nov-Dec;33(3-4):170-7
references.pmid: 19837564
references.citation: Arthritis Rheum. 2003 Apr;48(4):917-26
references.pmid: 12687533
references.citation: Arch Intern Med. 1990 Apr;150(4):785-7
references.pmid: 2109585
references.citation: J Eur Acad Dermatol Venereol. 2007 Sep;21(8):1108-9
references.pmid: 17714136
references.citation: Am J Respir Crit Care Med. 1999 Aug;160(2):736-55
references.pmid: 10430755
references.citation: Neuron. 2011 Oct 20;72(2):245-56
references.pmid: 21944778
references.citation: Curr Opin Immunol. 2009 Dec;21(6):596-605
references.pmid: 19896815
references.citation: PLoS Genet. 2009 Dec;5(12):e1000792
references.pmid: 20041220
references.citation: Arthritis Rheum. 2004 Mar;50(3):882-91
references.pmid: 15022331
references.citation: Genome Med. 2012 Jan 27;4(1):6
references.pmid: 22284131
references.citation: Neurology. 2011 Mar 15;76(11):1006-14
references.pmid: 21325651
references.citation: Arch Neurol. 2008 Nov;65(11):1533-5
references.pmid: 19001174
references.citation: Nat Rev Neurol. 2010 Apr;6(4):211-20
references.pmid: 20234357
references.citation: Arch Intern Med. 1985 Aug;145(8):1386-8
references.pmid: 4026469
references.citation: Cogn Behav Neurol. 2006 Dec;19(4):190-3
references.pmid: 17159614
references.citation: Nature. 2006 Aug 24;442(7105):916-9
references.pmid: 16862116
references.citation: J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1107-11
references.pmid: 15258209
references.citation: Neurobiol Aging. 2007 May;28(5):639-47
references.pmid: 16697488
references.citation: Clin Immunol Immunopathol. 1997 Sep;84(3):223-43
references.pmid: 9281381
references.citation: Genes Immun. 2011 Apr;12(3):176-82
references.pmid: 21326317
references.citation: Acta Neuropathol. 2011 Jul;122(1):111-3
references.pmid: 21644037
references.citation: Science. 2011 Apr 22;332(6028):478-84
references.pmid: 21393509
references.citation: Lancet. 1999 May 22;353(9166):1777-83
references.pmid: 10348006
references.citation: Am J Gastroenterol. 2000 Aug;95(8):1974-82
references.pmid: 10950045