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Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects

Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (M...

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Autores principales: Wang, Ruihan, Gao, Hui, Xie, Hongsheng, Jia, Zhiyun, Chen, Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424494/
https://www.ncbi.nlm.nih.gov/pubmed/36051222
http://dx.doi.org/10.3389/fneur.2022.933217
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author Wang, Ruihan
Gao, Hui
Xie, Hongsheng
Jia, Zhiyun
Chen, Qin
author_facet Wang, Ruihan
Gao, Hui
Xie, Hongsheng
Jia, Zhiyun
Chen, Qin
author_sort Wang, Ruihan
collection PubMed
description Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (MAPT), and the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which could cause neurodegenerative pathological changes years before symptom onset. Noninvasive quantitative molecular imaging with PET or single-photon emission CT (SPECT) allows for selective visualization of the molecular targets in vivo to investigate brain metabolism, perfusion, neuroinflammation, and pathophysiological changes. There was increasing evidence that several molecular imaging biomarkers tend to serve as biomarkers to reveal the early brain abnormalities in familial FTLD. Tau-PET with (18)F-flortaucipir and (11)C-PBB3 demonstrated the elevated tau position in patients with FTLD and also showed the ability to differentiate patterns among the different subtypes of the mutations in familial FTLD. Furthermore, dopamine transporter imaging with the (11)C-DOPA and (11)C-CFT in PET and the (123)I-FP-CIT in SPECT revealed the loss of dopaminergic neurons in the asymptomatic and symptomatic patients of familial FTLD. In addition, PET imaging with the (11)C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the (11)C-DAA1106 and (11)C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. (18)F-fluorodeoxyglucose (FDG)-PET indicated hypometabolism in FTLD with different mutations preceded the atrophy on MRI. Identifying molecular imaging biomarkers for familial FTLD is important for the in-vivo assessment of underlying pathophysiological changes with disease progression and future disease-modifying therapy. We review the recent progress of molecular imaging in familial FTLD with focused on the possible implication of these techniques and their prospects in specific mutation types.
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spelling pubmed-94244942022-08-31 Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects Wang, Ruihan Gao, Hui Xie, Hongsheng Jia, Zhiyun Chen, Qin Front Neurol Neurology Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (MAPT), and the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which could cause neurodegenerative pathological changes years before symptom onset. Noninvasive quantitative molecular imaging with PET or single-photon emission CT (SPECT) allows for selective visualization of the molecular targets in vivo to investigate brain metabolism, perfusion, neuroinflammation, and pathophysiological changes. There was increasing evidence that several molecular imaging biomarkers tend to serve as biomarkers to reveal the early brain abnormalities in familial FTLD. Tau-PET with (18)F-flortaucipir and (11)C-PBB3 demonstrated the elevated tau position in patients with FTLD and also showed the ability to differentiate patterns among the different subtypes of the mutations in familial FTLD. Furthermore, dopamine transporter imaging with the (11)C-DOPA and (11)C-CFT in PET and the (123)I-FP-CIT in SPECT revealed the loss of dopaminergic neurons in the asymptomatic and symptomatic patients of familial FTLD. In addition, PET imaging with the (11)C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the (11)C-DAA1106 and (11)C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. (18)F-fluorodeoxyglucose (FDG)-PET indicated hypometabolism in FTLD with different mutations preceded the atrophy on MRI. Identifying molecular imaging biomarkers for familial FTLD is important for the in-vivo assessment of underlying pathophysiological changes with disease progression and future disease-modifying therapy. We review the recent progress of molecular imaging in familial FTLD with focused on the possible implication of these techniques and their prospects in specific mutation types. Frontiers Media S.A. 2022-08-16 /pmc/articles/PMC9424494/ /pubmed/36051222 http://dx.doi.org/10.3389/fneur.2022.933217 Text en Copyright © 2022 Wang, Gao, Xie, Jia and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Wang, Ruihan
Gao, Hui
Xie, Hongsheng
Jia, Zhiyun
Chen, Qin
Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects
title Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects
title_full Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects
title_fullStr Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects
title_full_unstemmed Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects
title_short Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects
title_sort molecular imaging biomarkers in familial frontotemporal lobar degeneration: progress and prospects
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424494/
https://www.ncbi.nlm.nih.gov/pubmed/36051222
http://dx.doi.org/10.3389/fneur.2022.933217
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