Hippocampal sclerosis and TDP-43 in the population.
Research type
Research Study
Full title
Investigating the association of hippocampal sclerosis with TDP-43 in the population.
IRAS ID
164796
Contact name
Suvi R. K. Hokkanen
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Clinicaltrials.gov Identifier
Study ID 3026, UKCRN: Cambridge City over75s Cohort study (CC75C); 05Q0108308, NRES: CC75C
Duration of Study in the UK
0 years, 1 months, 0 days
Research summary
Dementia is a concern for our time, one consequence of the success in extending average human lifespans. An important cause of dementia among the older elderly may be hippocampal sclerosis (HScl) a condition about which very little is known. It is characterized by severe nerve cell loss in the part of the brain controlling memory processing. How this neuron loss develops, what it relates to, and how common HScl is, remain unclear.
HScl has been associated in autopsy-based studies with pathologies that accumulate with brain aging, including the TAR-DNA-binding protein-43 (TDP-43). Results from our pilot study based the longitudinal population-based clinicopathological Cambridge City over 75s Cohort (CC75C) indicate that in the general population, HScl is consistently associated with hippocampal TDP-43 pathology, and is independent from Alzheimer's Disease (AD) and vascular disease pathologies. The underlying aetiology of HScl might be associated with TDP-43.
In the CC75C cohort, ten out of 241 cases were not stained with antibodies against TDP-43 because the tissue blocks of the relevant areas were used up. However, several of these ten cases are of high interest to the project on HScl, as well as for any further project using the TDP-43 data in CC75C. Conserved tissue is still available, and it is possible to re-block and stain the areas of interest.
We aim to re-block the ten missing CC75C cases and analyze TDP-43 in these according to existing protocols in order to complete the CC75C TDP-43 data. This is of high importance, because TDP-43 appears to be a key pathology in late life dementia, and crucial to understand the underlying pathophysiology of HScl.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
14/EM/1241
Date of REC Opinion
10 Nov 2014
REC opinion
Favourable Opinion