PHAGO-PET
Research type
Research Study
Full title
PET imaging of microglia with flu vaccine challenge from TREM2 MCI/AD cohort
IRAS ID
221880
Contact name
Marios Politis
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
As some people get older small amounts of damage can accumulate in their brain and may cause brain immune cells to become faulty, which may in turn lead to greater brain inflammation and an increased risk of developing diseases such as Alzheimer’s disease. Our goal is to develop a treatment for Alzheimer’s disease by modulating how brain immune cells respond to damage. Our study aims to produce new knowledge and tools about brain inflammation to help us achieve this. We know that certain genetic factors can influence brain immune cell behaviour which we think may contribute to Alzheimer’s disease or related conditions. Understanding this better may provide important clues for directing our efforts to find a treatment. We will investigate levels of inflammation in the brains of people with and without Alzheimer’s disease and different genetic profiles using a special type of brain scan called positron emission tomography (PET) as well as take a sample of cerebrospinal fluid (CSF) to measure inflammatory markers (optional). PET imaging allows us to measure chemical changes within the brain and consequently study the functions of the brain. We will also carry out a magnetic resonance imaging (MRI) scan of the brain which will be used to help us with the analysis of the PET scan. All the subjects included will undergo the inoculation of the seasonal influenza vaccine and they will repeat after 5-7 days the PET scan for the inflammation.
Lay Summary of study results:
The main immune cells of the brain are called microglia. We investigated microglia response in older adults without dementia before and following flu vaccine. We made comparisons based on genes expressed in microglia and believed to be linked to dementia. We used a series of specialist brain scans, and a range of memory and thinking assessments.Participants with a version of the TREM2 gene ( p.R47H) had lower than expected microglia activity in areas known to be affected earlier in Alzheimer’s disease, despite having a similar amount of tau protein (a protein that collects with Alzheimer’s disease) expected to increase microglia activity. They also had certain areas of subtle reduced brain volume and had subtle differences in some areas of memory assessment.
This study expands our knowledge about the role of the immune system in the development of Alzheimer’s disease and supports the theory that microglia are initially protective in this condition. Future therapies are already in development to enhance the protective action of microglia.
REC name
London - Bloomsbury Research Ethics Committee
REC reference
17/LO/1266
Date of REC Opinion
7 Sep 2017
REC opinion
Further Information Favourable Opinion