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- W2980329483 abstract "Failed clinical trials for Alzheimer's disease (AD) suggest that Aβ aggregation must be targeted at very early disease stages to be effective. Furthermore, the deposition of amyloid per se, as assessed microscopically or via PET imaging, is likely to be a relatively late manifestation of the pathogenic process. It is not known when the initial, pre-amyloid Aβ seeds begin to form, propagate, and spread through the brain, nor has the structure of the initial Aβ seeds been defined. We tested a variety of well-described and clinically-tested antibodies for their in vivo recognition of pre-amyloid seeds in Aβ-precursor protein(APP)-transgenic mice. In parallel, we used immunoprecipitation of size-fractionated, native, brain-derived Aβ assemblies and established antibody recognition profiles to allow prediction of Aβ seed recognition. We identified at least one antibody (the murine version of aducanumab) that administered for only 5 consecutive days at pre-deposition stage, achieved long-lasting (50%) prevention of Aβ deposition and associated pathologies in APP-transgenic mice 6 months later. These findings demonstrate the presence of pathogenic Aβ seeds well before amyloid formation becomes detectable. Lowering such bioactive, pre-amyloid seeds maybe an effective paradigm for AD prevention." @default.
- W2980329483 created "2019-10-25" @default.
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- W2980329483 date "2019-07-01" @default.
- W2980329483 modified "2023-09-27" @default.
- W2980329483 title "P4‐689: INACTIVATION OF PATHOGENIC Aβ SEEDS AT PRE‐AMYLOID DISEASE STAGES" @default.
- W2980329483 doi "https://doi.org/10.1016/j.jalz.2019.09.054" @default.
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