
DOI . ORG {
}
Title[redir]:
Amyloid plaque formation precedes dendritic spine loss | Acta Neuropathologica
Description:
Amyloid-beta plaque deposition represents a major neuropathological hallmark of Alzheimer’s disease. While numerous studies have described dendritic spine loss in proximity to plaques, much less is known about the kinetics of these processes. In particular, the question as to whether synapse loss precedes or follows plaque formation remains unanswered. To address this question, and to learn more about the underlying kinetics, we simultaneously imaged amyloid plaque deposition and dendritic spine loss by applying two-photon in vivo microscopy through a cranial window in double transgenic APPPS1 mice. As a result, we first observed that the rate of dendritic spine loss in proximity to plaques is the same in both young and aged animals. However, plaque size only increased significantly in the young cohort, indicating that spine loss persists even many months after initial plaque appearance. Tracking the fate of individual spines revealed that net spine loss is caused by increased spine elimination, with the rate of spine formation remaining constant. Imaging of dendritic spines before and during plaque formation demonstrated that spine loss around plaques commences at least 4 weeks after initial plaque formation. In conclusion, spine loss occurs, shortly but with a significant time delay, after the birth of new plaques, and persists in the vicinity of amyloid plaques over many months. These findings hence give further hope to the possibility that there is a therapeutic window between initial amyloid plaque deposition and the onset of structural damage at spines.
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Keywords {🔍}
spine, plaques, spines, plaque, dendritic, article, google, scholar, amyloid, mice, cas, pubmed, loss, disease, months, alzheimers, fig, density, age, time, test, kinetics, formation, imaging, growth, dendrites, model, mouse, control, neurosci, dendrite, vivo, weeks, significant, lost, vicinity, pathology, transgenic, synaptic, size, twophoton, germany, anova, elimination, brain, image, tukeykramer, post, hoc, analysis,
Topics {✒️}
avoid laser-induced phototoxicity article download pdf synapse loss precedes synapse-related protein synaptophysin experience-dependent synaptic plasticity wilcoxon signed-rank test toxic amyloid-β species multicolor time-stamp reveals large dense-core vesicles open-skull cranial window β-amyloid plaque deposition abeta42-driven cerebral amyloidosis open access spires-jones tl search search translational brain research clinical brain research direct optical access β-amyloid plaque appearance maximum intensity projected wild-type control animals single time-point analysis full size image privacy choices/manage cookies plaque formation demonstrated related subjects microglial/amyloid interaction full access scheff sw dzne-german center single transgenic yfp wegenast-braun bm original author amyloid plaque formation maximum intensity projections age-matched control animals initial plaque formation fibrillar amyloid deposits filament tracer module dendritic spine formation amyloid plaque size dendritic spine loss german federal ministry amyloid plaque load amyloid plaque staining cerebral β-amyloidosis amyloid-beta plaques neurofibrillary tangle formation spine loss occurs imaging abeta plaques
Questions {❓}
- Fiala JC, Spacek J, Harris KM (2002) Dendritic spine pathology: cause or consequence of neurological disorders?
- We were especially interested in the chronology: Which event comes first, dendritic spine loss or plaque formation?
Schema {🗺️}
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headline:Amyloid plaque formation precedes dendritic spine loss
description:Amyloid-beta plaque deposition represents a major neuropathological hallmark of Alzheimer’s disease. While numerous studies have described dendritic spine loss in proximity to plaques, much less is known about the kinetics of these processes. In particular, the question as to whether synapse loss precedes or follows plaque formation remains unanswered. To address this question, and to learn more about the underlying kinetics, we simultaneously imaged amyloid plaque deposition and dendritic spine loss by applying two-photon in vivo microscopy through a cranial window in double transgenic APPPS1 mice. As a result, we first observed that the rate of dendritic spine loss in proximity to plaques is the same in both young and aged animals. However, plaque size only increased significantly in the young cohort, indicating that spine loss persists even many months after initial plaque appearance. Tracking the fate of individual spines revealed that net spine loss is caused by increased spine elimination, with the rate of spine formation remaining constant. Imaging of dendritic spines before and during plaque formation demonstrated that spine loss around plaques commences at least 4 weeks after initial plaque formation. In conclusion, spine loss occurs, shortly but with a significant time delay, after the birth of new plaques, and persists in the vicinity of amyloid plaques over many months. These findings hence give further hope to the possibility that there is a therapeutic window between initial amyloid plaque deposition and the onset of structural damage at spines.
datePublished:2012-09-21T00:00:00Z
dateModified:2012-09-21T00:00:00Z
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Alzheimer’s disease
Two-photon in vivo imaging
Dendritic spines
Amyloid plaque
Kinetics
Structural plasticity
Pathology
Neurosciences
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headline:Amyloid plaque formation precedes dendritic spine loss
description:Amyloid-beta plaque deposition represents a major neuropathological hallmark of Alzheimer’s disease. While numerous studies have described dendritic spine loss in proximity to plaques, much less is known about the kinetics of these processes. In particular, the question as to whether synapse loss precedes or follows plaque formation remains unanswered. To address this question, and to learn more about the underlying kinetics, we simultaneously imaged amyloid plaque deposition and dendritic spine loss by applying two-photon in vivo microscopy through a cranial window in double transgenic APPPS1 mice. As a result, we first observed that the rate of dendritic spine loss in proximity to plaques is the same in both young and aged animals. However, plaque size only increased significantly in the young cohort, indicating that spine loss persists even many months after initial plaque appearance. Tracking the fate of individual spines revealed that net spine loss is caused by increased spine elimination, with the rate of spine formation remaining constant. Imaging of dendritic spines before and during plaque formation demonstrated that spine loss around plaques commences at least 4 weeks after initial plaque formation. In conclusion, spine loss occurs, shortly but with a significant time delay, after the birth of new plaques, and persists in the vicinity of amyloid plaques over many months. These findings hence give further hope to the possibility that there is a therapeutic window between initial amyloid plaque deposition and the onset of structural damage at spines.
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Alzheimer’s disease
Two-photon in vivo imaging
Dendritic spines
Amyloid plaque
Kinetics
Structural plasticity
Pathology
Neurosciences
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