Cerebral amyloid induces aberrant axonal sprouting and ectopic terminal formation in amyloid precursor protein transgenic mice
| Autor: | Bernd Sommer, Martina Stalder, Mathias Jucker, Michael E. Calhoun, Michael Frotscher, Thomas Deller, Amie L. Phinney, Matthias Staufenbiel |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pathology
medicine.medical_specialty Amyloid BACE1-AS Hippocampus Mice Transgenic Biology Choristoma Axonal Transport Article Amyloid beta-Protein Precursor Mice Thalamus mental disorders medicine Amyloid precursor protein Animals Entorhinal Cortex Senile plaques Nerve Endings Neurons General Neuroscience P3 peptide Brain Entorhinal cortex Axons Biochemistry of Alzheimer's disease Mice Inbred C57BL nervous system Dentate Gyrus biology.protein |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 19(19) |
| ISSN: | 1529-2401 |
| Popis: | A characteristic feature of Alzheimer’s disease (AD) is the formation of amyloid plaques in the brain. Although this hallmark pathology has been well described, the biological effects of plaques are poorly understood. To study the effect of amyloid plaques on axons and neuronal connectivity, we have examined the axonal projections from the entorhinal cortex in aged amyloid precursor protein (APP) transgenic mice that exhibit cerebral amyloid deposition in plaques and vessels (APP23 mice). Here we report that entorhinal axons form dystrophic boutons around amyloid plaques in the entorhinal termination zone of the hippocampus. More importantly, entorhinal boutons were found associated with amyloid in ectopic locations within the hippocampus, the thalamus, white matter tracts, as well as surrounding vascular amyloid. Many of these ectopic entorhinal boutons were immunopositive for the growth-associated protein GAP-43 and showed light and electron microscopic characteristics of axonal terminals. Our findings suggest that (1) cerebral amyloid deposition has neurotropic effects and is the main cause of aberrant sprouting in AD brain; (2) the magnitude and significance of sprouting in AD have been underestimated; and (3) cerebral amyloid leads to the disruption of neuronal connectivity which, in turn, may significantly contribute to AD dementia. |
| Databáze: | OpenAIRE |
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