Again Tau tangles are unlikely to be causative, but a pathophysiological consequence of an upstream cause. I am no doctor, but I immediately want to ask things like; but would it not be logical that a disease like Alzheimer's spread along the energy highways of the brain leaving the protein in it's trail?
Instead some BPs will say hurrah we are on to something here, let's spend a few more billions with confidence we've got the culprit by it's short and curlies.