Related Experiment Videos
Dendrite and dendritic spine alterations in Alzheimer models
Donna L Moolman1, Ottavio V Vitolo, Jean-Paul G Vonsattel
1Taub Institute for Research on Alzheimer's Disease and the Aging Brain and Department of Pathology, Columbia University, New York, NY 10032, USA.
Journal of Neurocytology
|October 12, 2004
Summary
Alzheimer disease (AD) causes dementia by damaging synapses. Transgenic mice and human AD tissue show reduced dendritic spines and area, with abnormal neurites near, but not localized to, amyloid plaques.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Cell Biology
Background:
- Synaptic damage and loss are key contributors to dementia severity in Alzheimer disease (AD).
- Understanding neuronal morphology changes is crucial for AD research.
Purpose of the Study:
- To visualize and compare the neuronal morphology of transgenic mouse models of AD with wild-type controls.
- To investigate the relationship between amyloid plaques and neurite abnormalities in AD.
Main Methods:
- Multicolor DiOlistic labeling of hippocampal neurons to image dendritic arbors.
- Comparison of J20 and APP/PS1 transgenic mouse lines at various ages with wild-type littermates.
- Combined immunohistochemistry and DiOlistic labeling to co-localize amyloid-beta (Abeta) plaques and neurites.
Main Results:
- Transgenic mice exhibited swollen, bulbous dystrophic neurites with spine loss.
- Statistically significant reductions in spine number and total dendrite area were observed in both transgenic lines at 11 months.
- Similar morphological abnormalities were found in human AD hippocampal tissue.
- Dystrophic neurites were not preferentially localized near Abeta plaques, but reactive astrocytes were often found in plaque proximity.
Conclusions:
- Early-onset synaptic and dendritic abnormalities occur in APP/PS1 and J20 mouse models of AD.
- These findings in mouse models mirror human AD neuropathology.
- The study suggests that neurite pathology in AD may not be directly driven by plaque proximity.