MAPT and Alzheimer disease: Protein aggregates such as TDP-43 and C9ORF72 repeats in amyotrophic lateral sclerosis (ALS) [35], polyQ-expanded huntingtin in HD [36], hypo-phosphorylated tau and amyloid β in AD [37], α-synuclein in parkinson's disease (PD) [38] are generally removed via proteasomal machinery but excessive toxic overload of aggregates may expose cells to persistent oxidative stress.