Shortly after arriving at Houston Methodist in 2014, Masdeu took a bold step. He reported his findings that neurodegeneration in Alzheimer’s was associated with abnormal tau, a protein that forms inside cells from the normal tau that maintains the integrity of microtubules. At the time, most Alzheimer’s experimental therapies focused on the amyloid protein. But Masdeu did not find a similar association with the amyloid protein, also found in this disorder.

In April 2019, Masdeu pushed forward with the concept that abnormal tau may spread in the brain through the normal brain highways, the white matter tracts that connect brain hubs to each other in a complex network arrangement. His study, published in , is the first to demonstrate this concept  in humans. Using sophisticated neuroimaging, Masdeu and his team, particularly Belen Pascual, PhD, combined MRI and ¹⁸F-flortaucipir PET to study tau in a rare disease that affects the language-related syntactic brain network. The anterior node of this network, in the frontal lobe, was affected first. Sick neurons found here, containing tau, contacted and "infected” neurons in the separate, but connected, posterior node in the temporal lobe. The white matter tract connecting both nodes was affected, as would be expected when the neurons in the anterior node died first.