Treatment with simvastatin in patients with Alzheimer's disease lowers both alpha- and beta-cleaved amyloid precursor protein.
We investigated the clinical and biological effects of cholesterol-lowering treatment with a statin in 19 patients with Alzheimer's disease. They received simvastatin 20 mg/day for 12 weeks in an open trial. Primary efficacy parameters were the changes after 12 weeks in the cerebrospinal fluid (CSF) levels of beta-amyloid(42) (Abeta(42)), alpha-secretase-cleaved amyloid precursor protein (alpha-sAPP), beta-secretase-cleaved APP (beta-sAPP), tau, phospho-tau and the plasma levels of Abeta(42). A secondary efficacy parameter was the change in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog) score. After 12 weeks, CSF alpha-sAPP and CSF beta-sAPP were significantly reduced (p < 0.001), but the CSF levels of tau, phospho-tau, Abeta(42) and the plasma levels of Abeta(42) were unchanged. The ADAS-cog score was slightly increased (p < 0.05). The results suggest that simvastatin acts directly on the processing of APP by inhibiting both the alpha- and the beta-secretase pathways.
Sjögren
Magnus
M
Institute of Clinical Neuroscience, Göteborg University, Sahlgrenska University Hospital/Mölndal, SE-431 80 Mölndal, Sweden. magnus.sjogren@medfak.gu.se
Gustafsson
Kina
K
Syversen
Steinar
S
Olsson
Annika
A
Edman
Ake
A
Davidsson
Pia
P
Wallin
Anders
A
Blennow
Kaj
K
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D019821:Simvastatin / Q000008:administration & dosage*
D016564:Amyloid beta-Protein Precursor; D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019821:Simvastatin