Fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β-amyloid pathology
Neurodegeneration, accumulation of β-amyloid (Aβ) plaques, and neuroinflammation are the major hallmarks of Alzheimer's disease. Here, we aimed to investigate the temporal and spatial association between synaptic activity, Aβ plaque load, and neuroinflammation in an Aβ mouse model with limited...
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| Language: | English |
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Elsevier
2025-04-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811925001673 |
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| author | L.H. Kunze G. Palumbo J. Gnörich K. Wind-Mark R. Schaefer S. Lindner F.-J. Gildehaus S. Ziegler M. Brendel |
| author_facet | L.H. Kunze G. Palumbo J. Gnörich K. Wind-Mark R. Schaefer S. Lindner F.-J. Gildehaus S. Ziegler M. Brendel |
| author_sort | L.H. Kunze |
| collection | DOAJ |
| description | Neurodegeneration, accumulation of β-amyloid (Aβ) plaques, and neuroinflammation are the major hallmarks of Alzheimer's disease. Here, we aimed to investigate the temporal and spatial association between synaptic activity, Aβ plaque load, and neuroinflammation in an Aβ mouse model with limited neurodegeneration.26 APPSL70 and 15 C57Bl/6 mice underwent longitudinal PET-scans with [18F]UCB-H from plaque onset to levels of strong plaque load (5.3 - 11.0 months of age) to assess the synaptic vesicle protein 2A (SV2A) expression, [18F]FBB to determine the fibrillar Aβ plaque load, and [18F]GE-180 and [18F]F-DED to assess microglial and astroglial (re)activity. Statistical parametric mapping was performed to uncover similarities between the binding patterns of all four tracers.We found a continuous increase in Aβ-PET in APPSL70 mice from 5.3 to 11.0 months of age, resulting in a significantly higher [18F]FBB PET signal in the cortex, hippocampus, and thalamus of APPSL70 mice compared to C57Bl/6 mice at 11.0 months of age. Parallel increases in SV2A-PET signals were observed in the cortex and thalamus of APPSL70 mice compared to C57Bl/6 mice. Statistical parametric mapping revealed a similar pattern of Aβ- and SV2A-PET differences (dice coefficient 53 %). Patterns of microglia activation showed stronger congruency with SV2A expression (dice coefficient 58 %) than patterns of reactive astrogliosis (dice coefficient 26 %).APPSL70 mice with limited neurodegeneration comprise a close temporal and spatial association between SV2A expression, Aβ plaque load, and microglial activation. SV2A PET imaging in APPSL70 mice may facilitate longitudinal monitoring of increased synaptic activity in the earliest phase of AD. |
| format | Article |
| id | doaj-art-54a82db5e4df4b44bc9794d52a3ba7a7 |
| institution | OA Journals |
| issn | 1095-9572 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj-art-54a82db5e4df4b44bc9794d52a3ba7a72025-08-20T01:54:11ZengElsevierNeuroImage1095-95722025-04-0131012116510.1016/j.neuroimage.2025.121165Fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β-amyloid pathologyL.H. Kunze0G. Palumbo1J. Gnörich2K. Wind-Mark3R. Schaefer4S. Lindner5F.-J. Gildehaus6S. Ziegler7M. Brendel8Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, GermanyDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, GermanyDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, GermanyDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, GermanyDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, GermanyDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, GermanyDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, GermanyDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany; Department of Nuclear Medicine, Hannover Medical School (MHH), Hannover, GermanyDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilian University of Munich, 81377 Munich, Germany; Corresponding author at: Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany.Neurodegeneration, accumulation of β-amyloid (Aβ) plaques, and neuroinflammation are the major hallmarks of Alzheimer's disease. Here, we aimed to investigate the temporal and spatial association between synaptic activity, Aβ plaque load, and neuroinflammation in an Aβ mouse model with limited neurodegeneration.26 APPSL70 and 15 C57Bl/6 mice underwent longitudinal PET-scans with [18F]UCB-H from plaque onset to levels of strong plaque load (5.3 - 11.0 months of age) to assess the synaptic vesicle protein 2A (SV2A) expression, [18F]FBB to determine the fibrillar Aβ plaque load, and [18F]GE-180 and [18F]F-DED to assess microglial and astroglial (re)activity. Statistical parametric mapping was performed to uncover similarities between the binding patterns of all four tracers.We found a continuous increase in Aβ-PET in APPSL70 mice from 5.3 to 11.0 months of age, resulting in a significantly higher [18F]FBB PET signal in the cortex, hippocampus, and thalamus of APPSL70 mice compared to C57Bl/6 mice at 11.0 months of age. Parallel increases in SV2A-PET signals were observed in the cortex and thalamus of APPSL70 mice compared to C57Bl/6 mice. Statistical parametric mapping revealed a similar pattern of Aβ- and SV2A-PET differences (dice coefficient 53 %). Patterns of microglia activation showed stronger congruency with SV2A expression (dice coefficient 58 %) than patterns of reactive astrogliosis (dice coefficient 26 %).APPSL70 mice with limited neurodegeneration comprise a close temporal and spatial association between SV2A expression, Aβ plaque load, and microglial activation. SV2A PET imaging in APPSL70 mice may facilitate longitudinal monitoring of increased synaptic activity in the earliest phase of AD.http://www.sciencedirect.com/science/article/pii/S1053811925001673Synaptic densityAlzheimer's diseaseSV2A-PETβ-amyloid |
| spellingShingle | L.H. Kunze G. Palumbo J. Gnörich K. Wind-Mark R. Schaefer S. Lindner F.-J. Gildehaus S. Ziegler M. Brendel Fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β-amyloid pathology NeuroImage Synaptic density Alzheimer's disease SV2A-PET β-amyloid |
| title | Fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β-amyloid pathology |
| title_full | Fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β-amyloid pathology |
| title_fullStr | Fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β-amyloid pathology |
| title_full_unstemmed | Fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β-amyloid pathology |
| title_short | Fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β-amyloid pathology |
| title_sort | fibrillar amyloidosis and synaptic vesicle protein expression progress jointly in the cortex of a mouse model with β amyloid pathology |
| topic | Synaptic density Alzheimer's disease SV2A-PET β-amyloid |
| url | http://www.sciencedirect.com/science/article/pii/S1053811925001673 |
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