Investigating the role of neuroinflammation on the accumulation and spread of tau pathology.

Lead Research Organisation: University of Southampton
Department Name: Centre for Biological Sciences

Abstract

Many studies have investigated the effect of inflammation on amyloid pathology, yet its effect on the severity of tau pathology remains understudied. Tau is a microtubule associated protein which in AD becomes hyperphosphorylated and accumulates in neurons to form NFTs. Unlike amyloid plaques, the severity of NFT pathology in AD correlates with cognitive decline. In AD patients, NFT pathology progresses in a stereotypical pattern affecting the entorhinal cortex first, followed by the hippocampus and finally spreading to the neocortex. The progressive accumulation and spread of tau pathology has been replicated in animal models. We have shown that systemic inflammation, induced by intraperitoneal injection of LPS or real life bacteria (Salmonella typhimurium) accelerates ongoing CNS disease via activation of endothelial cells and microglia and a recent clinical study showed 5-fold faster decline in cognitive function when serum levels of pro-inflammatory cytokines are elevated after exposure to a systemic infection. These studies suggest that sustained low grade systemic inflammation is a major risk factor for earlier onset of disease.
In this collaborative study we aim to test the hypothesis that systemic inflammation accelerates the accumulation and spread of tau pathology thus contributing to disease pathogenesis.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/N018133/1 02/10/2016 01/04/2021
1789834 Studentship MR/N018133/1 01/10/2016 30/09/2020 Sarah Howard
 
Description ARUK South Coast Network Equipment Grant
Amount £2,615 (GBP)
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2020 
End 01/2020
 
Description Alzheimer's Research UK Conference grant
Amount £452 (GBP)
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2018 
End 04/2018
 
Description British Neuropathological Society Small Postgraduate Grant
Amount £3,903 (GBP)
Organisation British Neuropathological Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2021 
End 07/2021
 
Description British Neuropathological Society Small Postgraduate Grant
Amount £4,908 (GBP)
Organisation British Neuropathological Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2019 
End 12/2020
 
Description Guarantors of Brain Travel Grant
Amount £1,000 (GBP)
Organisation Guarantors of Brain 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2018 
End 04/2018
 
Description Alzheimer's Research UK South Coast Network Cafe Scientifique 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Supporters
Results and Impact The Café Scientifique was organised by the ARUK South Coast network to bring patients, carers, fundraisers and researchers together. Several speakers discussed their fundraising efforts and the importance of raising money for research into Alzheimer's disease. We then sat at tables related to our area of research and the public rotated between research groups. Our table was focused on the role of neuroinflammation in Alzheimer's disease. We spoke to many people about our work and why we believe it is important for developing therapies for this neurodegenerative disease. It was a very interesting chance to speak to people who care for patients with Alzheimer's disease and how they are coping. The event increased awareness for the work that ARUK do and enabled the public to speak to researchers who have had projects funded by their charitable donations.
Year(s) Of Engagement Activity 2018
URL https://www.alzheimersresearchuk.org/network-centres/south-coast-network-centre/
 
Description The New Forest Show 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The New Forest Show is visitied by approximately 95,000 people over three days (as of 2017). We ran a stall amongst other research groups from the University of Southampton. The aim of our stall is to engage the public, both young and old, and introduce them to our research. We had interactive activities for children and spoke to parents about our research and why it was important for the public to have greater awareness. Many people showed significant interest in our research examining the role of neuroinflammation in neurodegenerative disease. To be able to reach such a large audience is rare and makes the New Forest show such a useful venue to engage with the general public.
Year(s) Of Engagement Activity 2017