Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. One of the major neuropathological hallmarks is the accumulation of the extracellular senile plaques that are mainly composed of amyloid beta (Aβ) protein. Plaques are associated with synapse loss, dystrophic neurites and altered neurite trajectories. A reversal of such morphological changes has been observed days after single dose anti-Aβ immunotherapy. In this study we investigated the extended effects of a single dose of passive anti-Aβ immunotherapy on morphological changes associated with senile plaques. We found that although plaque burden was not reduced 30 days after immunotherapy, there were fewer dystrophic neurites around each plaque, a recovery of synapse density, and normalization of neurite curvature near plaques. Taken together these results suggest that a single dose of immunotherapy is sufficient to cause lasting benefits to the morphology of cortical neurons, implying substantial plasticity of neural circuits despite the continued presence of plaques.
Bibliographical noteFunding Information:
This work was supported by NIH grants AG08487, a John D French Foundation Fellowship, the Alzheimer's Disease Drug Discovery Foundation, and Alzheimer's Association Pioneer Award and grant EB00768. We also thank Elan for providing antibodies (3D6 and 12E8).
- Senile plaque
- Synaptic plasticity