TDP-43 frontotemporal lobar degeneration and autoimmune disease.
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.


DESIGN
Case control.


SETTING
Academic medical centres.


PARTICIPANTS
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.


OUTCOME MEASURES
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.
['Miller|Zachary A|ZA|', 'Rankin|Katherine P|KP|', 'Graff-Radford|Neill R|NR|', 'Takada|Leonel T|LT|', 'Sturm|Virginia E|VE|', 'Cleveland|Clare M|CM|', 'Criswell|Lindsey A|LA|', 'Jaeger|Philipp A|PA|', 'Stan|Trisha|T|', 'Heggeli|Kristin A|KA|', 'Hsu|Sandy Chan|SC|', 'Karydas|Anna|A|', 'Khan|Baber K|BK|', 'Grinberg|Lea T|LT|', 'Gorno-Tempini|Maria Luisa|ML|', 'Boxer|Adam L|AL|', 'Rosen|Howard J|HJ|', 'Kramer|Joel H|JH|', 'Coppola|Giovanni|G|', 'Geschwind|Daniel H|DH|', 'Rademakers|Rosa|R|', 'Seeley|William W|WW|', 'Wyss-Coray|Tony|T|', 'Miller|Bruce L|BL|']
D000368:Aged D000544:Alzheimer Disease D018888:Aphasia, Primary Progressive D001327:Autoimmune Diseases D015331:Cohort Studies D004522:Educational Status D005260:Female D057174:Frontotemporal Lobar Degeneration D006801:Humans D007249:Inflammation D036341:Intercellular Signaling Peptides and Proteins D016015:Logistic Models D008297:Male D008875:Middle Aged D009154:Mutation D009483:Neuropsychological Tests D015995:Prevalence D000077153:Progranulins D011569:Psychiatric Status Rating Scales D057177:TDP-43 Proteinopathies D014409:Tumor Necrosis Factor-alpha
DEMENTIA EPIDEMIOLOGY IMMUNOLOGY RHEUMATOLOGY