Tau Protein Modifications May Be Linked to Heterogeneity in Alzheimer's Disease

A study in Nature Medicine led by Massachusetts General Hospital researchers examined tau proteins as a factor in variance of Alzheimer's Disease (AD) progression in different people, reports News-Medical . The researchers examined samples from 32 persons diagnosed with "typical AD" while living, which was confirmed postmortem. The age at diagnosis and the rate of AD progression differed significantly among this cohort. The team also performed an in-depth characterization of the molecular features of tau proteins within subjects' brains, and discovered "striking" variation in the presence of phosphorylated tau oligomers that are linked to greater tau spread and worse disease. Different modifications were connected to different degrees of severity and progression rate, and led to variable recognition by antibodies that are under consideration for the therapeutic targeting of tau proteins in AD and associated disorders. "We speculate that there are different molecular 'drivers' of Alzheimer's progression, with each patient having their own set of these," said Bradley Hyman at the Massachusetts General Institute for Neurodegenerative Disease. "This is similar to what we see in cancer, where there are several types of lung or breast cancer, for example, and the treatment depends on the particular molecular drivers in the patient's tumor."