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Tytuł:
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In vivo PET imaging of neuroinflammation in familial frontotemporal dementia.
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Autorzy:
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Malpetti M; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.
Rittman T; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.
Jones PS; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.
Cope TE; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.
Passamonti L; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.; Istituto di Bioimmagini e Fisiologia Molecolare Consiglio Nazionale delle Ricerche, Milan, Italy.
Bevan-Jones WR; Department of Psychiatry, University of Cambridge, Cambridge, Cambridgeshire, UK.
Patterson K; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.
Fryer TD; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.; Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, Cambridgeshire, UK.
Hong YT; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.; Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, Cambridgeshire, UK.
Aigbirhio FI; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK.; Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, Cambridgeshire, UK.
O'Brien JT; Department of Psychiatry, University of Cambridge, Cambridge, Cambridgeshire, UK.
Rowe JB; Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK .; Medical Research Council Cognition and Brain Sciences Unit, Cambridge, Cambridgeshire, UK.
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Źródło:
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Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2021 Mar; Vol. 92 (3), pp. 319-322. Date of Electronic Publication: 2020 Oct 29.
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Typ publikacji:
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Case Reports; Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: London : BMJ Publishing Group
Original Publication: London : British Medical Association
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MeSH Terms:
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Frontotemporal Dementia/*diagnostic imaging
Frontotemporal Dementia/*pathology
Aged ; C9orf72 Protein/genetics ; Female ; Frontotemporal Dementia/genetics ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; Progranulins/genetics ; tau Proteins/genetics
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References:
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Grant Information:
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MR/K02308X/1 United Kingdom MRC_ Medical Research Council; MR/P01271X/1 United Kingdom MRC_ Medical Research Council; MR/M009041/1 United Kingdom MRC_ Medical Research Council; 103838 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; MR/M024873/1 United Kingdom MRC_ Medical Research Council
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Contributed Indexing:
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Keywords: PET; frontotemporal dementia; genetics
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Substance Nomenclature:
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0 (C9orf72 Protein)
0 (GRN protein, human)
0 (MAPT protein, human)
0 (Progranulins)
0 (tau Proteins)
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Entry Date(s):
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Date Created: 20201030 Date Completed: 20210914 Latest Revision: 20240207
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Update Code:
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20240207
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PubMed Central ID:
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PMC7892378
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DOI:
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10.1136/jnnp-2020-323698
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PMID:
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33122395
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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 [ 11 C]PK11195, and the regional distribution of tau or TDP-43 pathology, indexed using the radioligand [ 18 F]AV-1451. The familial FTD PET data were compared with healthy controls.
Results: Patients with familial FTD across all mutation groups showed increased [ 11 C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [ 18 F]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.
Competing Interests: Competing interests: JBR reports consultancy unrelated to the work with Biogen, UCB, Asceneuron and Althira; and receipt of research grants from Janssen, AZ-Medimmune, Lilly unrelated to this work. JTO has provided consultancy to TauRx, Axon, Roche, GE Healthcare and Lilly; and has research awards from Alliance Medical and Merck. TR has received honoraria from the National Institute for Health and Clinical Excellence, Oxford Biomedica and Learna Ltd.
(© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)
Comment in: J Neurol Neurosurg Psychiatry. 2021 Mar;92(3):231. (PMID: 33361412)
