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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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.933217/full |
| _version_ | 1811215265257488384 |
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| author | Ruihan Wang Hui Gao Hongsheng Xie Zhiyun Jia Qin Chen |
| author_facet | Ruihan Wang Hui Gao Hongsheng Xie Zhiyun Jia Qin Chen |
| author_sort | Ruihan Wang |
| collection | DOAJ |
| 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 18F-flortaucipir and 11C-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 11C-DOPA and 11C-CFT in PET and the 123I-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 11C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the 11C-DAA1106 and 11C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. 18F-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. |
| first_indexed | 2024-04-12T06:18:41Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-12T06:18:41Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-ce02e58f1e4a4be8bbea23eb57b16dbb2022-12-22T03:44:23ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-08-011310.3389/fneur.2022.933217933217Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospectsRuihan Wang0Hui Gao1Hongsheng Xie2Zhiyun Jia3Qin Chen4Department of Neurology, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Neurology, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Neurology, West China Hospital of Sichuan University, Chengdu, ChinaFamilial 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 18F-flortaucipir and 11C-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 11C-DOPA and 11C-CFT in PET and the 123I-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 11C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the 11C-DAA1106 and 11C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. 18F-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.https://www.frontiersin.org/articles/10.3389/fneur.2022.933217/fullfamilial frontotemporal lobar degenerationmolecular imagingbiomarkersMAPTGRNC9orf72 |
| spellingShingle | Ruihan Wang Hui Gao Hongsheng Xie Zhiyun Jia Qin Chen Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects Frontiers in Neurology familial frontotemporal lobar degeneration molecular imaging biomarkers MAPT GRN C9orf72 |
| 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 | familial frontotemporal lobar degeneration molecular imaging biomarkers MAPT GRN C9orf72 |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.933217/full |
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