Treatment of Alzheimer's disease with clioquinol

Dement Geriatr Cogn Disord. 2001 Nov-Dec;12(6):408-14. doi: 10.1159/000051288.

Abstract

As heavy metal ions may be implicated in the formation of senile plaques in Alzheimer-afflicted brains, treatment with clioquinol was tested in 20 patients with Alzheimer's disease. Clioquinol is a chelator that crosses the blood-brain barrier and has greater affinity for zinc and copper ions than for calcium and magnesium ions. Treatment was given for 21 days at doses of 20 mg/day to 10 patients and 80 mg/day to another 10 patients. The study was blind to the dosages but included no controls. Cerebrospinal fluid (CSF) investigations revealed a significant increase at day 7 and a decrease at day 21 in Tau protein and growth-associated protein (GAP43). These proteins are increased in Alzheimer's disease and considered as rather stable markers. The initial increase may indicate a temporary cytotoxicity to the brain and/or an increased release into the CSF from stores in the tissue, possibly from senile plaques where the proteins are accumulated. The levels of CSF-Tau protein correlated positively and significantly with the serum levels of copper and also with the serum copper/zinc ratio. Clinical ratings showed slight improvement after 3 weeks treatment with clioquinol in this open study.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / drug therapy*
  • Chelating Agents / administration & dosage
  • Chelating Agents / adverse effects
  • Chelating Agents / therapeutic use*
  • Chelation Therapy / methods
  • Clioquinol / administration & dosage
  • Clioquinol / adverse effects
  • Clioquinol / therapeutic use*
  • Copper / blood
  • Dose-Response Relationship, Drug
  • Female
  • GAP-43 Protein / cerebrospinal fluid
  • GAP-43 Protein / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Treatment Outcome
  • Zinc / blood
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / drug effects*

Substances

  • Chelating Agents
  • GAP-43 Protein
  • tau Proteins
  • Copper
  • Clioquinol
  • Zinc