Distinct Effects of Testosterone on Plasma and Cerebrospinal Fluid Amyloid-β Levels

The effect of testosterone on the levels of the Alzheimer's disease amyloid- β peptide (Aβ) was investigated in guinea pigs. Castrated guinea pigs (GPX) were administered testosterone at two different dosages, following which plasma and cerebrospinal fluid (CSF) A β40 levels were measured. Plasma Aβ40 levels were reduced in GPX in the early stages of low-dose testosterone treatment, whereas CSF Aβ40 levels were only reduced by the time circulating testosterone had returned to untreated GPX levels. The supraphysiological testosterone dose did not reduce CSF Aβ40 levels significantly until circulating testosterone was back to uncastrated levels, whereas plasma Aβ40 levels significantly increased over time in these animals. These results indicate that the extent of testosterone-induced changes to Aβ40 levels and their response rates depend on both the tissue examined and testosterone dosage.