There is so much known about the Tau protein but we still have a lot to understand about its role in diseases. In disorders where Tau is the major protein that is involved – the primary taupathies – such as Pick’s disease and Progressive supranuclear palsy, it is clear that Tau has a major effect on the disease.
Tau is normally a unfolded, soluble, microtubule associated protein. It is encoded by MAPT gene and alternative splicing produces six isoforms of tau protein in the brain. There are 6 isoforms: The picture from this link:https://encyclopedia.pub/entry/39084

Abnormal post-translational modification is another major reason thought be a biomarker and key change for tau associated with Alzhiemer’s.
Also note: that in healthy humans the 3R and 4R isoforms are present in about equal amounts, but later in Alzheimer’s, this ratio changes ande 4R isoforms tends to aggregate.