Investigators have discovered a mechanism behind the spread of neurofibrillary tangles – one of the two hallmarks of Alzheimer’s disease – through the brains of affected individuals. In a report in the journal Nature Communications, researchers describe finding that a particular version of the tau protein, while extremely rare even in the brains of patients with Alzheimer’s disease, is able to spread from one neuron to another and how that process occurs.

“It has been postulated that tangles – the abnormal accumulation of tau protein that fills neurons in Alzheimer’s disease – can travel from neuron to neuron as the disease progresses, spreading dysfunction through the brain as the disease progresses. But how that happens has been uncertain,” said Bradley Hyman, M.D., Ph.D., director of the Massachusetts General Hospital  (MGH) Alzheimer’s Disease Research Center and senior author of the report. “Our current study suggests one mechanism at play is that a unique and rare type of tau has the properties we were looking for – it is released from neurons, taken up by other neurons, transported up and down axons, and then released again.”

The current study revealed that, when brain samples from that mouse model were applied to cultured neurons, only 1 percent of the tau in those samples was taken up by the neurons. The tau proteins that were taken up were high molecular weight – meaning that a number of smaller proteins are bound together into a larger molecule – soluble, and studded with a large number of phosphate molecules, a known characteristic of the tau in Alzheimer’s-associated tangles.  Similar results were seen in experiments using brain samples from Alzheimer’s patients, both in cultured neurons and in living mice.

Source: Massachusetts General Hospital


Massachusetts General Hospital News
Nature Communications

December 15, 2015