Tau proteins promote microtubule assembly via interaction with tubulin. Tau proteins were thought to be neuron-specific, and the abnormal accumulation of tau into neurofibrillary tangles in the brain is associated with Alzheimer disease. However, a high-molecular-weight isoform of tau (known as big tau) is also expressed in healthy and diseased hearts in humans. “Given the importance of microtubules for cardiomyocyte structure and function, the diastolic dysfunction phenotype we had previously described in the hearts of patients with Alzheimer disease, and the link between the tubulin code and heart failure with preserved ejection fraction (HFpEF), it was a natural hypothesis to test the involvement of tau in cardiomyopathy,” states Federica del Monte, senior investigator on the study.