Although the progression of amyloid deposition was sharply arrested by this approach, we found that a substantial amyloid burden remained even after long periods of transgene suppression. We examined a small number of animals after 12 mo of dox treatment (beginning at 6 mo of age), and found that amyloid deposits were still relatively abundant. Longer-term treatments are now in progress. At the latest treatment interval analyzed by ELISA, animals administered dox for 6 mo showed elevated levels of PBS-soluble Aβ (see Figure 5) that could be interpreted as an indication that the plaques are slowly releasing peptide (or oligomeric Aβ) into the soluble pool and might eventually dissolve. Whether inhibiting Aβ production longer than 6 (or 12) mo may ultimately result in clearance of amyloid is under investigation; unfortunately, the life span of the model eventually limits this experiment. Therapeutics used in humans will have considerably more time to act than is possible within the life span of rodent models. Long-term treatments would certainly be possible and could be a key to effective therapy. Overall, however, we interpret our findings as evidence that AD therapies that significantly lower the production of Aβ (by either inhibiting secretase activity or inhibiting APP expression) may not quickly reverse preexisting pathology, but should effectively halt further deposition of amyloid.