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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/27737
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dc.contributor.authorCousins, O-
dc.contributor.authorSchubert, JJ-
dc.contributor.authorChandra, A-
dc.contributor.authorVeronese, M-
dc.contributor.authorValkimadi, P-
dc.contributor.authorCreese, B-
dc.contributor.authorKhan, Z-
dc.contributor.authorArathimos, R-
dc.contributor.authorHampshire, A-
dc.contributor.authorRosenzweig, I-
dc.contributor.authorBallard, C-
dc.contributor.authorCorbett, A-
dc.contributor.authorAasland, D-
dc.contributor.authorVelayudhan, L-
dc.contributor.authorO’Neill, M-
dc.contributor.authorCollier, D-
dc.contributor.authorAwais, R-
dc.contributor.authorSander, K-
dc.contributor.authorÅrstad, E-
dc.contributor.authorHowes, O-
dc.contributor.authorTurkheimer, F-
dc.contributor.authorHodges, A-
dc.date.accessioned2023-11-25T19:39:04Z-
dc.date.available2023-11-25T19:39:04Z-
dc.date.issued2023-11-21-
dc.identifierORCID iD: Byron Creese https://orcid.org/0000-0001-6490-6037-
dc.identifier272-
dc.identifier.citationCousins, O. et al. (2023) 'Microglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challenge', Journal of Neuroinflammation, 20 (1), 272, pp. 1 - 13. doi: 10.1186/s12974-023-02945-0.en_US
dc.identifier.urihttps://bura.brunel.ac.uk/handle/2438/27737-
dc.descriptionAvailability of data and materials: The datasets used and analysed during the current study are available from the corresponding author on reasonable request.en_US
dc.descriptionSupplementary information is available online at: https://link.springer.com/article/10.1186/s12974-023-02945-0#Sec20 .-
dc.description.abstractCopyright © The Author(s) 2023. Background: Microglia are increasingly understood to play an important role in the pathogenesis of Alzheimer’s disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer’s disease. TREM2 is a microglial cell surface receptor. In this multi-modal/multi-tracer PET/MRI study we investigated the effect of TREM2 p.R47H carrier status on microglial activation, tau and amyloid deposition, brain structure and cognitive profile. Methods: We compared TREM2 p.R47H carriers (n = 8; median age = 62.3) and participants with mild cognitive impairment (n = 8; median age = 70.7). Participants underwent two [18F]DPA-714 PET/MRI scans to assess TSPO signal, indicative of microglial activation, before and after receiving the seasonal influenza vaccination, which was used as an immune stimulant. Participants also underwent [18F]florbetapir and [18F]AV1451 PET scans to assess amyloid and tau burden, respectively. Regional tau and TSPO signal were calculated for regions of interest linked to Braak stage. An additional comparison imaging healthy control group (n = 8; median age = 45.5) had a single [18F]DPA-714 PET/MRI. An expanded group of participants underwent neuropsychological testing, to determine if TREM2 status influenced clinical phenotype. Results: Compared to participants with mild cognitive impairment, TREM2 carriers had lower TSPO signal in Braak II (P = 0.04) and Braak III (P = 0.046) regions, despite having a similar burden of tau and amyloid. There were trends to suggest reduced microglial activation following influenza vaccine in TREM2 carriers. Tau deposition in the Braak VI region was higher in TREM2 carriers (P = 0.04). Furthermore, compared to healthy controls TREM2 carriers had smaller caudate (P = 0.02), total brain (P = 0.049) and white matter volumes (P = 0.02); and neuropsychological assessment revealed worse ADAS-Cog13 (P = 0.03) and Delayed Matching to Sample (P = 0.007) scores. Conclusions: TREM2 p.R47H carriers had reduced levels of microglial activation in brain regions affected early in the Alzheimer’s disease course and differences in brain structure and cognition. Changes in microglial response may underlie the increased Alzheimer’s disease risk in TREM2 p.R47H carriers. Future therapeutic agents in Alzheimer’s disease should aim to enhance protective microglial actions.en_US
dc.description.sponsorshipThis project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115976. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This project received funding and access to the [18F]florbetapir and [18F]AV1451 PET tracers from Avid and Lilly UK. Avid and Lilly UK were not involved in data analysis and interpretation. This project has received funding from the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. This research was supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. This research was supported by researchers at the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A partnership between UCL and University College London Hospitals NHS Foundation Trust. This work was funded in part through the MRC Proximity to Discovery: Industry Engagement Fund (External Collaboration, Innovation and Entrepreneurism: Translational Medicine in Exeter 2 (EXCITEME2) ref. MC_PC_17189) awarded to Dr Creese and MRC grant MR/N015746/1.en_US
dc.format.extent1 - 13-
dc.format.mediumElectronic-
dc.languageEnglish-
dc.language.isoen_USen_US
dc.publisherBioMed Central (part of Springer Nature)en_US
dc.rightsCopyright © The Author(s) 2023. Rights and permissions: Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subjectTREM2en_US
dc.subjectneuroinflammationen_US
dc.subjectTSPOen_US
dc.subjectFlorbetapiren_US
dc.subjectAV1451en_US
dc.subjectDPA714en_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectmicrogliaen_US
dc.subjectPETen_US
dc.titleMicroglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challengeen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1186/s12974-023-02945-0-
dc.relation.isPartOfJournal of Neuroinflammation-
pubs.issue1-
pubs.publication-statusPublished online-
pubs.volume20-
dc.identifier.eissn1742-2094-
dc.rights.holderThe Author(s)-
Appears in Collections:Dept of Life Sciences Research Papers

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