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Tau Present in Synapses of Post-Mortem Brains With Alzheimer Disease

Jolynn Tumolo

In addition to transmitting signals through the brain, synapses appear to be transporting tau in people with Alzheimer disease, according to study findings published online ahead of print in the journal Neuron.

“We have known for over 30 years that tangles spread through the brain during Alzheimer disease, but how they spread has remained a mystery,” said lead researcher and corresponding author Tara Spires-Jones, PhD, of the University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute in Edinburgh. 

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Evidence from mouse models of Alzheimer disease has suggested the possibility of the trans-synaptic spread of tau, according to the study. In particular, researchers reported evidence that tau oligomers, small clumps of tau protein, jumped from one side of the synapse to the other, which over time spread tau throughout the brain.

To investigate synaptic tau accumulation in humans, researchers used powerful microscopy techniques that allowed them to visualize proteins from more than 1 million synapses from 42 post-mortem brains. They found tau oligomers present in the synapses of people who died from Alzheimer disease. Tangles of tau oligomers were inside both ends of the synapse: the brain cell sending signals as well as the brain cell receiving signals, researchers reported.

They believe reducing oligomeric tau at synapses could be a promising therapeutic approach against Alzheimer disease progression.

“Wherever tangles appear in the brain, neuron death follows, contributing to the decline in cognitive ability,” said Dr Spires-Jones. “Stopping the spread of toxic tau is a promising strategy to stop the disease in its tracks.”

 

References

Colom-Cadena M, Davies C, Sirisi S, et al. Synaptic oligomeric tau in Alzheimer's disease - a potential culprit in the spread of tau pathology through the brain. Neuron. Published online ahead of print May 10, 2023. doi:10.1016/j.neuron.2023.04.020

Dementia study reveals how toxic proteins spread through brain. News release. University of Edinburgh; May 15, 2023. Accessed June 23, 2023.

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