Amyloid hypothesis assumes that extracellular beta-amyloid (Aβ) aggregation is the top of the pathological cascade of Alzheimer's disease, and therefore nothing should occur before extracellular Aβ aggregation. According to the theory, neuronal cell death is the result of this extracellular Aβ aggregation. However, results in this study indicate that intracellular Aβ accumulation induces YAP-dependent necrosis of neurons before formation of extracellular Aβ plaque. Therefore, extracellular Aβ aggregation is not the cause but the result of neuronal death in Alzheimer's disease. Meanwhile, the data do not exclude that extracellular Aβ aggregation is also toxic secondarily.
Department of Neuropathology,
Medical Research Institute and Center for Brain Integration Research,