MAPT and neurodegenerative disease: Protein aggregation and misfolding are recurrent in many neurodegenerative diseases (i.e. Parkinson's, Alzheimer's, etc.).126 The relationship between the metal ions and protein aggregation is difficult to describe precisely because even a slight change of the external environment (pH, metal ion/protein concentration, etc.) can disrupt the fragile equilibrium state of the functional protein.126 The disorderliness of Tau and α-synuclein, for example, is context specific,127 including in the presence of metal ions.