Passive immunotherapy rapidly increases structural plasticity in a mouse model of Alzheimer disease.
Senile plaque-associated changes in neuronal connectivity such as altered neurite trajectory, dystrophic swellings, and synapse and dendritic spine loss are thought to contribute to cognitive dysfunction in Alzheimer's disease and mouse models. Immunotherapy to remove amyloid beta is a promising therapy that causes recovery of neurite trajectory and dystrophic neurites over a period of days. The acute effects of immunotherapy on neurite morphology at a time point when soluble amyloid has been cleared but dense plaques are not yet affected are unknown. To examine whether removal of soluble amyloid beta (Abeta) has a therapeutic effect on dendritic spines, we explored spine dynamics within 1 h of applying a neutralizing anti Abeta antibody. This acute treatment caused a small but significant increase in dendritic spine formation in PDAPP brain far from plaques, without affecting spine plasticity near plaques or average dendritic spine density. These data support the hypothesis that removing toxic soluble forms of amyloid-beta rapidly increases structural plasticity possibly allowing functional recovery of neural circuits.
Spires-Jones
Tara L
TL
MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, MA, USA.
Mielke
Matthew L
ML
Rozkalne
Anete
A
Meyer-Luehmann
Melanie
M
de Calignon
Alix
A
Bacskai
Brian J
BJ
Schenk
Dale
D
Hyman
Bradley T
BT
D000544:Alzheimer Disease / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D001921:Brain / Q000648:ultrastructure; D049229:Dendritic Spines / Q000648:ultrastructure*; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D009474:Neurons / Q000648:ultrastructure*; D058225:Plaque, Amyloid / Q000473:pathology
D016229:Amyloid beta-Peptides