A multi-institutional study led by Harvard Medical School investigators based at Massachusetts General Hospital and researchers from Johns Hopkins University School of Medicine has found how the abnormal form of tau, which accumulates in the neurofibrillary tangles that characterize Alzheimer’s disease, can disrupt the normal function of brain cells.
In their report published in the journal Neuron, the team describes how tau interferes with communication between the nucleus of neurons and the rest of the cell body, called the cytoplasm.
“Communication between the nucleus and the rest of the cell is usually a tightly regulated process,” said co-senior author Bradley Hyman, the HMS John B. Penney, Jr. Professor of Neurology at Mass General.
“Our work shows a new way tau might cause brain cells to become impaired. In other systems, disruption of this communication causes cell misfunction and even cell death, so we think this might contribute to neuronal dysfunction and death in Alzheimer’s disease as well,” he added.
Prior research by Hyman’s team had discovered a newly identified biochemical feature of tau—that under certain circumstances it can form microscopic droplets. A search for other proteins with this property led the investigators to the proteins of the nuclear pore complex, a structure on the nuclear membrane that controls the passage of proteins and RNA between the nucleus and the cytoplasm.
In the current study, they set out to investigate whether and how tau might interact with proteins in the nuclear pore complex, which contains 30 different proteins called nucleoporins that form the channel through which molecules move.