Figure 2.

In vivo treatment of guinea pigs with simvastatin reduced total Aβ, Aβ40, and Aβ42 levels in guinea pig CSF. Aβ levels recovered after treatment was stopped. CSF was collected at day 0 and 3 from guinea pigs. After this, animals were given a simvastatin-containing diet and CSF samples were drawn twice weekly. (a) After 3 weeks simvastatin-containing food was replaced by standard diet. Aβ levels declined for the first 3 weeks and recovered subsequently. In control animals Aβ levels remained constant (n = 5). (b) In a second experiment animals were treated as before for 3 weeks. A continuous decline in all Aβ levels was found. In control animals Aβ levels remained constant. For clarity, Aβ42 and Aβ40 levels of control animals are given in a and Aβ42 and Aβ40 level measurement was extended for control animals to 6 weeks as in the previous experiment (n = 6). (c) Western blot determination of CSF Aβ levels after 3 weeks of treatment. (d) Aβ tissue levels. Aβ was precipitated with W02 antibody from detergent-lysed cortex samples. Simvastatin-treated animals showed a strong reduction of brain tissue Aβ levels equivalent to the reduction observed in the CSF in a (n = 4). Mean level of control animals was set to 100% (±22% SD; n = 6). As expected from the CSF results, the recovery animals had normal Aβ levels (n = 6). The reduction in treated as compared with control animals was significant (P = 0.012).