Peters F, Salihoglu H, Rodrigues E, Herzog E, Blume T, Filser S, Dorostkar M, Shimshek DR, Brose N, Neumann U, Herms J. BACE1 inhibition more effectively suppresses initiation than progression of β-amyloid pathology. Acta Neuropathol. 2018 May;135(5):695-710. Epub 2018 Jan 11 PubMed.
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Washington University School of Medicine
The work by Peters et. al is beautiful and comprehensive in quantitation of plaque growth and formation. They clearly demonstrated better efficacy of the β-secretase inhibitor before individual plaque formation, suggesting that treating during a period of new plaque formation, or even before, will be most effective. This would translate to the 10–20 years before symptom onset in DIAN.
A caveat of the work is that the mouse model overexpresses Aβ production, so the concentrations and kinetics may not replicate typical human plaque growth.
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