Statin treatment and a disease-specific pattern of beta-amyloid peptides in Alzheimer's disease.
According to the amyloid cascade hypothesis, sporadic Alzheimer's disease (AD) is caused by the production and aggregation of beta-amyloid (Abeta), and the production of Abeta has recently been linked to the metabolism of cholesterol. We have previously published clinical studies where the effect of statin treatment on Abeta production has been investigated. No effect on Abeta was found, which is in disagreement with cell and animal studies. In the present study we investigated the effect of statin treatment on a disease-specific pattern consisting of a C-terminally-truncated quintet of Abeta peptides. Nineteen patients with AD were treated with simvastatin for 12 months and the quintet of Abeta peptides were analysed in cerebrospinal fluid before and after treatment. Also included was a group of 15 untreated patients with AD. We found that the Abeta peptide pattern at baseline was in agreement with earlier findings; however, we did not find any change in the Abeta peptide pattern after statin treatment. We suggest that clinical studies with extended treatment periods are performed where higher dosages of statins are used. We also believe that the pleiotropic effects of statins should be investigated further in order to elucidate the connection between Alzheimer's disease and statin treatment.
Höglund
Kina
K
Institute of Clinical Neuroscience, Section of Experimental Neurochemistry, Göteborg University, Neurolabb, SU/Mölndal, 43180, Mölndal, Sweden. kina.hoglund@neuro.gu.se
Syversen
Steinar
S
Lewczuk
Piotr
P
Wallin
Anders
A
Wiltfang
Jens
J
Blennow
Kaj
K
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000187:drug effects; D010455:Peptides / Q000134:cerebrospinal fluid / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42); D019821:Simvastatin