MAPT and Alzheimer disease: The adult human brain expresses multiple main tau isoforms, which can be categorized as 3R or 4R tau based on whether they contain three or four carboxy-terminal repeat domains.32 3R and 4R tau is more common in Alzheimer’s disease, while 4R tau is seen in diseases such as progressive supranuclear palsy.33 To determine which isoform exists in the substantia nigra, the 3R and 4R isoforms were examined and co-localized with AT8-labelled phosphorylated tau.