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Thakker DR, Sankaranarayanan S, Weatherspoon MR, Harrison J, Pierdomenico M, Heisel JM, Thompson LA, Haskell R, Grace JE, Taylor SJ, Albright CF, Shafer LL. Centrally Delivered BACE1 Inhibitor Activates Microglia, and Reverses Amyloid Pathology and Cognitive Deficit in Aged Tg2576 Mice. J Neurosci. 2015 Apr 29;35(17):6931-6. PubMed.
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German Center for Neurodegenerative Diseases (DZNE)
I am particularly intrigued to see that the BACE1 inhibitor still has such a strong effect in old mice where amyloid pathology is already heavily visible. Currently, we think that amyloid-lowering drugs may have their strongest effect in a preventive but not a therapeutic approach. While we do not know whether a 17-month-old Tg2576 mouse (as tested here) corresponds to a presymptomatic or a symptomatic human individual, the study suggests that a BACE1 inhibitor may still be helpful at later stages in the pathogenesis. This supports testing BACE1 inhibitors not only in preventive trials but also in clinical trials with patients in early symptomatic phases, such as MCI (as currently underway).
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