New study reveals how toxic proteins spread through brain in Alzheimer’s

New research led by Prof Tara Spires-Jones (UK DRI at Edinburgh) has revealed fresh insight into the spread of damaging proteins that build up in the brains of people with Alzheimer’s disease. Researchers say the study, published in the journal Neuron, could hold the key to stopping the condition progressing.

Large clumps of the protein tau – called tangles – form in brain cells and are one of the defining features of Alzheimer’s. As these tangles spread through the brain during the disease there is a decline in brain function.

The new study, which also included scientists from the University of Edinburgh, the Institut d'Investigacions Biomèdiques Hospital de Sant Pau and the Institute for Advanced Chemistry of Catalonia (Barcelona), focused on synapses, the connections between brain cells. During the progression of Alzheimer’s, synapses are lost and this is strongly linked to reduced memory and thinking abilities.

In the study, scientists examined more than one million synapses from 42 people using powerful microscopy techniques to visualise proteins within individual synapses.

The team discovered that small clumps of the protein tau – known as tau oligomers – are found within the synapses of people who died of Alzheimer’s disease. Tangles of tau oligomers were seen inside both sides of the synapse – from the neuron sending signals and the neuron receiving signals.

In a mouse model of the disease, the oligomers jumped from one side of the synapse to the other, spreading the toxic tau through the brain. Lowering oligomeric tau at synapses may be a promising strategy to stop disease progression in future, experts say.

Prof Spires-Jones said:

“We have known for over 30 years that tangles spread through the brain during Alzheimer’s disease, but how they spread has remained a mystery. Wherever tangles appear in the brain, neuron death follows, contributing to the decline in cognitive ability. Stopping the spread of toxic tau is a promising strategy to stop the disease in its tracks.”

To find out more about Prof Tara Spires-Jones’ work, visit her UK DRI profile. To stay up to date on the latest research news and institute updates, sign up to receive our monthly newsletter, ‘Inside Eye on UK DRI’.

Reference: Colom-Cadena, M. et al. (2023) ‘Synaptic oligomeric tau in alzheimer’s disease — a potential culprit in the spread of tau pathology through the brain’, Neuron. doi:10.1016/j.neuron.2023.04.020.

Article published: 15 May 2023
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