The cognitive and neurochemical effects of the acetylcholinesterase inhibitor ENA713 on apolipoprotein E-deficient mice

S. Chapman, E. Grauer, Y. Chen, E. Shohami, M. Weinstock, D. M. Michaelson

Research output: Contribution to journalArticlepeer-review


Alzheimer's disease (AD) is associated with marked degeneration of basal forebrain cholinergic projections. This resulted in investigations of the efficacy of cholinomimetic treatments in AD and the observations that centrally acting acetylcholinesterase (ACHE) inhibitors, such as ENA713, can be used for alleviating some of the symptoms of AD. Genetic studies revealed that the allele E4 of apolipoprotein E (apoE) is a major risk factor of AD and that the extent of cholinergic degeneration in AD is related to the patients' apoE genotype. This led to the suggestion that apoE plays an important and specific role in brain cholinergic function. Studies utilizing apoE-deficient mice revealed that they have distinct working memory impairments which are associated with specific loss of synapses of the basal forebrain cholinergic pathways which project to the cortex and the hippocampus. Furthermore, it was shown that cholinomimetic treatment utilizing an M1 muscarinic agonist results in amelioration of the cognitive and presynaptic cholinergic deficits of apoE-deficient mice. In the present study we examined whether the cognitive and neurochemical deficits of the apoE-deficient mice can be reversed by cholinomimetic treatment utilizing the centrally acting AChE inhibitor ENA713. This revealed that prolonged treatment of the apoE-deficient mice with ENA713 completely reversed their behavioral deficit. However, unlike treatment with an M1 muscarinic agonist, ENA713 did not change the brain AChE levels of the apoE-deficient mice but rather caused a decrease in the brain AChE levels of the controls.

Original languageEnglish
Pages (from-to)171-175
Number of pages5
JournalInternational Journal of Geriatric Psychopharmacology
Issue number3
StatePublished - 1998


  • Acetylcholinesterase
  • Apolipoprotein E
  • Apolipoprotein E knockout mice
  • ENA 713
  • Mice


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