MAPT and early-onset autosomal dominant Alzheimer disease: In general, a crowded physiological environment could play an important role in the pathogenesis of Alzheimer disease by accelerating Tau protein misfolding [13,14] and Aβ misfolding [17,63,64], in the pathogenesis of prion diseases by accelerating amyloidogenic PrP oligomerization and misfolding [13–15,53,54] and inducing human PrP fibril fragmentation [13], in the pathogenesis of Parkinson disease by accelerating α-synuclein misfolding [19–22,59], and in the pathogenesis of ALS by accelerating SOD1 misfolding [14].