Amygdala TDP-43 pathology in the population
Research type
Research Study
Full title
Amygdala TDP-43 pathology in the population
IRAS ID
210449
Contact name
Carol Brayne
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and The University of Cambridge
Clinicaltrials.gov Identifier
MREC: CFAS, Ref. 99/5/22, 05/MRE05/37
Duration of Study in the UK
0 years, 5 months, 16 days
Research summary
The pathophysiology of dementia is still poorly understood. Most of the dementing disorders present with deposits of abnormal deposits in the brain, for example Alzheimer’s disease (AD) with the proteins tau and A-beta. Pathological protein deposits are thought to be key to the clinical manifestation of dementia. Accumulations of a protein called TDP-43 is the major neuropathological characteristic of the most common type of frontotemporal dementia, but is also frequent in AD (up to 70% of the cases). In the general elderly population, TDP-43 is present in 27% of the cases.
Within AD, TDP-43 pathology is shown to make the cognitive presentation and decline worse. TDP-43 is postulated to first affect a brain region called the amygdala, and then to follow a pattern that has been summarized in a TDP-43 staging scheme. The amygdala has central roles in memory processing, decision-making and emotional response. It is not known if this TDP-43 staging pattern is also observed in the population and other diseases.
The research project “Significance of TDP-43 in the European population in relation to dementia and associated symptomology and neuropathology”, led by Dr. Keage and Prof. Brayne 2009-2011, investigated the importance of TDP-43 in two UK cohorts that have population-representation and brain donation after death (CFAS and CC75C). TDP-43 was initially meant to be assessed in several brain regions, including the hippocampus, temporal cortex, and amygdala. Unfortunately, because of budget constraints, the amygdala had to be omitted.
Scientifically, staining of the amygdala would be hugely valuable. It would significantly add to our knowledge on TDP-43 prevalence, understanding of TDP-43 pathophysiology, and pathways underlying the clinical manifestation of dementia.
There is now funding available to stain the amygdala of ca 400 cases in the CFAS cohort.
REC name
HSC REC B
REC reference
16/NI/0189
Date of REC Opinion
31 Aug 2016
REC opinion
Favourable Opinion