Treatment of Alzheimer's disease with clioquinol.
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.
Regland
B
B
Institute of Clinical Neuroscience, Göteborg University, Sahlgrenska University Hospital/Mölndal, SE-431 80 Mölndal, Sweden. bjorn.regland@vgregion.se
Lehmann
W
W
Abedini
I
I
Blennow
K
K
Jonsson
M
M
Karlsson
I
I
Sjögren
M
M
Wallin
A
A
Xilinas
M
M
Gottfries
C G
CG
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D002614:Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000379:methods; D007464:Clioquinol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003300:Copper / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D019922:GAP-43 Protein / Q000134:cerebrospinal fluid / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D015032:Zinc / Q000097:blood; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000187:drug effects*
D002614:Chelating Agents; D019922:GAP-43 Protein; D016875:tau Proteins; D003300:Copper; D007464:Clioquinol; D015032:Zinc