For the first time, researchers have observed tau proteins, one of the presumed causes of Alzheimer’s disease, spreading from neuron to neuron in a manner similar to how an infection might advance in tissue.
The research, published in the journal Brain, put the idea of "transneuronal spread" to the test by looking at the distribution of tau proteins compared to the distribution of functional connections in the brain of patients with Alzheimer’s disease.
“If the idea of transneuronal spread is correct, then the areas of the brain that are most highly connected should have the largest build-up of tau and will pass it on to their connections,” lead author Dr Thomas Cope, from the Department of Clinical Neurosciences at the University of Cambridge, said in a statement. “It’s the same as we might see in a flu epidemic, for example – the people with the largest networks are most likely to catch flu and then to pass it on to others. And this is exactly what we saw.”
Transneuronal spread is one of three competing hypotheses that explain the distribution of tau proteins. The "metabolic vulnerability" hypothesis suggests that tau proteins are made in nerve cells and the more efficient producers are the ones that suffer from it. The "trophic support" hypothesis instead suggests that certain areas of the brain are more susceptible than others due to a lack of nutrition. However, the team's observations couldn’t find support for either of these two ideas.
Alzheimer’s disease is believed to be caused by the progressive accumulation of two types of proteins – amyloid beta and tau. Both are responsible for the formation of clumps in sufferers’ brains. The accumulation of amyloid beta proteins creates plaque outside brain cells, while tau proteins accumulate inside neurons. Tau proteins end up inhibiting or even killing brain cells in this way.
"In Alzheimer’s disease, the most common brain region for tau to first appear is the entorhinal cortex area, which is next to the hippocampus, the 'memory region,'" Professor James Rowe, senior author on the study, explained. "This is why the earliest symptoms in Alzheimer’s tend to be memory problems. But our study suggests that tau then spreads across the brain, infecting and destroying nerve cells as it goes, causing the patient’s symptoms to get progressively worse."
Understanding how tau spreads across the brain could be important for future therapies. Such research could help develop drugs that can halt tau proteins before they advance across large areas of the brain. It is estimated that 44 million people worldwide have Alzheimer’s disease.