Acetylcholinesterase inhibitors for Alzheimer's disease: anti-inflammatories in acetylcholine clothing!

Age Ageing. 2006 Jul;35(4):336-8. doi: 10.1093/ageing/afl027.

Abstract

The pathogenesis of Alzheimer's disease (AD) has been linked to a deficiency in the brain neurotransmitter acetylcholine. Subsequently, acetylcholinesterase inhibitors (AChEIs) were introduced for the symptomatic treatment of AD. The prevailing view has been that the efficacy of AChEIs is attained through their augmentation of acetylcholine-medicated neuron to neuron transmission. However, AChEIs also protect cells from free radical toxicity and beta-amyloid-induced injury, and increased production of antioxidants. In addition, it has been reported that AChEIs directly inhibit the release of cytokines from microglia and monocytes. These observations are supported by evidence showing a role for acetylcholine in suppression of cytokine release through a 'cholinergic anti-inflammatory pathway'. Based on the accumulating research data so far, it is no longer appropriate to consider that the sole action of AChEIs in AD is through direct acetylcholine-medicated enhancement of neuronal transmission. Evidence points to a possible anti-inflammatory role for these agents as well.

MeSH terms

  • Acetylcholine / physiology*
  • Aged
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / etiology
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use*
  • Cytokines / metabolism
  • Humans
  • Neurotransmitter Agents / physiology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cholinesterase Inhibitors
  • Cytokines
  • Neurotransmitter Agents
  • Acetylcholine