APP and Alzheimer disease: Although the causal role of NFTs in neurodegeneration of tauopathies is still questionable, for example, the neurons with NFTs can live for years [3], and the mutations of amyloid precursor protein (APP) [4] and presenilins [5] are accused of the pathogenesis of AD, the neuronal toxicity of NFTs have been implicated by a number of studies in cellular and animal tauopathy models [2].