A single dose of passive immunotherapy has extended benefits on synapses and neurites in an Alzheimer's disease mouse model.
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 (Abeta) 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-Abeta immunotherapy. In this study we investigated the extended effects of a single dose of passive anti-Abeta 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.
Rozkalne
Anete
A
MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, MA 02129, USA.
Spires-Jones
Tara L
TL
Stern
Edward A
EA
Hyman
Bradley T
BT
D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001323:Autoantibodies; D001369:Axons / Q000276:immunology / Q000473:pathology; D001921:Brain / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000276:immunology* / Q000473:pathology; D058225:Plaque, Amyloid / Q000276:immunology / Q000473:pathology; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics; D013569:Synapses / Q000276:immunology* / Q000473:pathology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001323:Autoantibodies; D058255:Protease Nexins; D011956:Receptors, Cell Surface