Amyloid-beta antibody treatment leads to rapid normalization of plaque-induced neuritic alterations

J Neurosci. 2003 Nov 26;23(34):10879-83. doi: 10.1523/JNEUROSCI.23-34-10879.2003.

Abstract

The accumulation of amyloid-beta into insoluble plaques is a characteristic feature of Alzheimer's disease. Neuronal morphology is distorted by plaques: rather than being essentially straight, they are substantially more curved than those in control tissue, their trajectories become altered, and they are frequently distended or swollen, presumably affecting synaptic transmission. Clearance of plaques by administration of antibodies to amyloid-beta is a promising therapeutic approach to the treatment of Alzheimer's disease, leading to stabilization of dementia by an unknown cellular mechanism. The effect of plaque clearance on plaque-induced neuronal alterations has not been studied previously. Here we show that both plaques and neuritic lesions are reversible in a strikingly short period of time after administration of a single dose of amyloid-beta antibody. Amyloid clearance and recovery of normal neuronal geometries were observed as early as 4 d and lasted at least 32 d after a single treatment. These results demonstrate that, once plaques are cleared, neuronal morphology is self-correcting and that passive antibody treatment has the potential to reverse neuronal damage caused by Alzheimer's disease and, hence, directly impact cognitive decline. Moreover, the rapid normalization of neuritic dystrophy suggests an unexpected degree of plasticity in the adult nervous system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / immunology*
  • Animals
  • Antibodies / therapeutic use*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / immunology
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Drug Administration Routes
  • Humans
  • Immunization, Passive / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurites / drug effects*
  • Neurites / immunology
  • Neurites / pathology
  • Neuronal Plasticity / drug effects
  • Plaque, Amyloid / drug effects*
  • Plaque, Amyloid / immunology
  • Plaque, Amyloid / pathology
  • Treatment Outcome

Substances

  • Amyloid beta-Peptides
  • Antibodies