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In vivo PET imaging of neuroinflammation in familial frontotemporal dementia.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Jones, Peter Simon 
Cope, Thomas Edmund 
Passamonti, Luca 

Abstract

INTRODUCTION: We report in vivo patterns of neuroinflammation and abnormal protein aggregation in seven cases of familial frontotemporal dementia (FTD) with mutations in MAPT, GRN and C9orf72 genes. METHODS: Using positron emission tomography (PET), we explored the association of the distribution of activated microglia, as measured by the radioligand [11C]PK11195, and the regional distribution of tau or TDP-43 pathology, indexed using the radioligand [18F]AV-1451. The familial FTD PET data were compared with healthy controls. RESULTS: Patients with familial FTD across all mutation groups showed increased [11C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [18F]AV-1451 binding across the brain, with heterogeneous distributions among carriers of GRN and C9orf72 mutations. DISCUSSION: This case series suggests that neuroinflammation is part of the pathophysiology of familial FTD, warranting further consideration of immunomodulatory therapies for disease modification and prevention.

Description

Keywords

PET, frontotemporal dementia, genetics, Aged, C9orf72 Protein, Female, Frontotemporal Dementia, Humans, Male, Middle Aged, Positron-Emission Tomography, Progranulins, tau Proteins

Journal Title

J Neurol Neurosurg Psychiatry

Conference Name

Journal ISSN

0022-3050
1468-330X

Volume Title

92

Publisher

BMJ

Rights

All rights reserved
Sponsorship
Wellcome Trust (103838/Z/14/Z)
Medical Research Council (MR/P01271X/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Medical Research Council (MR/M009041/1)
Medical Research Council (MR/M024873/1)
Medical Research Council (MR/K02308X/1)
This study was co-funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre; the Wellcome Trust (103838); the Medical Research Council (MR/P01271X/1); a Cambridge Trust & Sidney Sussex College Scholarship; and the Cambridge Centre for Parkinson-Plus. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.