Treatment with Simvastatin in Patients with Alzheimer’s Disease Lowers Both α- and β-Cleaved Amyloid Precursor Protein

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Abstract
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 β-amyloid42 (Aβ42), α-secretase-cleaved amyloid precursor protein (α-sAPP), β-secretase-cleaved APP (β-sAPP), tau, phospho-tau and the plasma levels of Aβ42. A secondary efficacy parameter was the change in the Alzheimer’s Disease Assessment Scale-Cognition (ADAS-cog) score. After 12 weeks, CSF α-sAPP and CSF β-sAPP were significantly reduced (p < 0.001), but the CSF levels of tau, phospho-tau, Aβ42 and the plasma levels of Aβ42 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 α- and the β-secretase pathways.