Alternative Therapy of Alzheimer's Disease via Supplementation With Choline Acetyltransferase

Neurosci Lett. 2004 Sep 30;368(3):258-62. doi: 10.1016/j.neulet.2004.05.116.

Abstract

Much evidence indicates that the memory and cognitive deficits of patients with Alzheimer's disease are closely associated with dysfunction of central cholinergic system. The degree of reduction of choline acetyltransferase activity in cerebral cholinergic neurons is significantly correlated with the severity of dementia or cognitive impairments observed in Alzheimer's disease. Therefore, Alzheimer's disease may be slowed by supplementation of exogenous choline acetyltransferase. Here we show that choline acetyltransferase mediated by TAT protein transduction domain passes through the blood-brain barrier and enters the neurons in mice, increasing choline acetyltransferase and neurotransmitter acetylcholine contents. The recombination TAT-choline acetyltransferase fusion protein injected intravenously improves the memory and cognitive dysfunction in Alzheimer's disease model mice induced by amyloid-beta peptide. Our results imply a novel and potentially effective way for Alzheimer's disease therapy.

Publication types

  • Comparative Study

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / enzymology*
  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / enzymology
  • Choline O-Acetyltransferase / administration & dosage*
  • Choline O-Acetyltransferase / biosynthesis
  • Complementary Therapies / methods*
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Humans
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice

Substances

  • Choline O-Acetyltransferase