MAPT and Alzheimer disease: In the healthy brain, the 3R and 4R isoforms are equivalently expressed.46 In Alzheimer’s brain, there is a decrease in 3R tau isoform or increase in 4R tau levels resulting in shift in the ratio of 4R-tau to 3R-tau.47,48 Our observation demonstrated that light 3R and intense 4R labelled neurons observed in substantia nigra of MMD and PD were similar to a pattern that existed in temporal cortex of Alzheimer’s disease (Supplementary Fig. 6), indicating that unequal 3R and 4R tau expression was associated with neurodegeneration.