Subclinical semantic deficits in autoimmune conditions. Version 1
Research type
Research Study
Full title
Screening for evidence of mild semantic impairment as a marker of underlying TDP-43 neuropathology in autoimmune conditions.
IRAS ID
147320
Contact name
Peter Garrard
Contact email
Sponsor organisation
St George's, University of London
Research summary
A link has recently been proposed between autoimmunity (the underlying mechanism of diseases such as rheumatoid arthritis or systemic lupus erythematosus) and one of the two main pathological subtypes of frontotemporal dementia (FTLD). In most cases of FTLD, neuropathology is characterised by one of two patterns: deposition of tau or TDP-43 protein. The disease mechanisms are poorly understood: each pattern can be associated with a genetic mutation, but the majority of cases are sporadic. The mutation that gives rise to TDP-43 deposition is in GRN, the protein product of which -progranulin - has anti-inflammatory properties. TDP-43 almost always underpins the clinical syndrome of semantic dementia (SD), which is therefore a reliable clinical marker of the pathology. A recent screen of patients with autoimmunity for novel autoantibodies revealed progranulin as a frequent antibody target in a variety of autoimmune conditions, raising the possibility of a link between autoimmunity and TDP-43 pathology. The proposed link was supported by the finding of a higher-than-expected prevalence of autoimmune disease among patients suspected of harbouring TDP-43 pathology on genetic (GRN mutation) or clinical (SD) grounds. We will use sensitive tests of semantic memory to look for the existence of mild deficits in patients with a common autoimmune condition - rheumatoid arthritis (RA). We will measure blood levels of progranulin and TNF-alpha (a marker of inflammatory activity) to look for evidence of mechanistic link.
REC name
London - Bromley Research Ethics Committee
REC reference
14/LO/0320
Date of REC Opinion
28 Jul 2014
REC opinion
Further Information Favourable Opinion