Infection and Dementia (Version 1.0)
Research type
Research Study
Full title
Neutrophil derived microvesicles: linking systemic inflammation and dementia.
IRAS ID
246642
Contact name
Daniel J Blackburn
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS FT
Clinicaltrials.gov Identifier
STH sponsor R&D registration number, STH20325
Duration of Study in the UK
0 years, 8 months, 31 days
Research summary
Research summary
Many carers of people with dementia often notice that symptoms get worse following an infection. This suggests that systemic inflammation (inflammation in the body resulting from infection or injury) has direct effects on brain function and accelerates dementia. Systemic inflammation is associated with a large increase in the number of circulating neutrophils, which are the most abundant white blood cell. Neutrophils produce large numbers of small pouch-like vesicles which impact the function of blood vessels in the body. Endothelial cells lining blood vessels in the brain are normally very tightly linked together but in Alzheimer’s disease they become leaky, allowing the movement of damaging substances into the brain. Our research has shown that the vesicles produced by neutrophils enter human brain endothelial cells, affecting their leakiness, and that they contain small molecules which are able to control gene expression. We plan to recruit healthy control and patients with dementia to compare the levels of neutrophil-derived vesicles in their blood, and to develop a robust method to examine the content of these vesicles. Understanding how systemic inflammation contributes to dementia is essential to identify new therapeutic treatments.Summary of results
Patients with dementia often become more impaired and deteriorate quicker following an infection, suggesting that infection has direct effects on brain function. Infection is associated with an increase in the number of circulating white blood cells, the most abundant of which are neutrophils. These cells can produce large numbers of small sacs known as microvesicles, which affect the function of blood vessels and contain small molecules called microRNAs that control gene expression. The cells lining blood vessels in the brain (called endothelial cells) are normally very tightly linked together, controlling what can move across this barrier, but in Alzheimer's disease they become leaky, allowing the movement of damaging substances into the brain. In this study we examined the content of microvesicles, and found 15 miRNAs that were significantly different in patients with dementia. These altered miRNAs were linked to several important biological pathways that affect how brain endothelial cells work and communicate. This research suggests that changes in miRNAs in dementia patients might contribute to increased blood-brain barrier damage and brain inflammation during infections, potentially worsening cognitive decline. Understanding these mechanisms could help in developing new treatments to protect brain health in dementia patients.REC name
Wales REC 5
REC reference
18/WA/0188
Date of REC Opinion
21 May 2018
REC opinion
Favourable Opinion