Alzheimer's-Associated Tau Protein Disrupts Molecular Transport Within Neurons

A study published in Neuron clarifies how the abnormal tau protein that clumps in the neurofibrillary tangles that characterize Alzheimer's disease can disrupt the normal function of neurons, reports ScienceDaily . Under certain conditions, tau can cohere into microscopic droplets and interact with proteins in the nuclear pore complex. Using people with Alzheimer's and cellular models of tau-based neuropathology, the researchers determined the Alzheimer's-associated form of tau directly interacts with the nucleoporin known as Nup98, causing it to be mislocated into the cytoplasm and promote tau accumulation in neurofibrillary tangles. The nuclei of neurons from individuals with Alzheimer's also took up large test molecules, suggesting leakage in nuclear pore complexes. The structures also contracted in number and became unevenly distributed throughout the nuclear membrane. Neurons from mice genetically coded to develop tau brain tangles exhibited similar leakage, allowing large dye molecules to pass into the nuclei. "If we can block the interaction between tau and the nuclear pore, it might allow existing neurons to become more functional in subjects; so one of our next steps will be determining whether or not that is possible," says Massachusetts Alzheimer's Disease Research Center Professor Bradley Hyman.