Edinburgh team show how Alzheimer’s spreads

In collaboration with Spanish and Catalan researchers, the Edinburgh team have discovered that synapses – connections used to carry essential signals throughout the brain – are also transporting tau proteins.

These tau proteins are considered toxic due to their impact on the synapses and researchers think that intercepting their transport and build up in the brain may present a “promising strategy” for Alzheimer’s disease.

The synapses – junctions between nerves – in the brain are vital communication vessels which support healthy brain function by enabling the flow of chemical and electrical messages between brain cells.

Large clumps of the tau protein, known as ‘tangles’, form in the brain cells and are one of the defining features of Alzheimer’s disease. The spread of these tangles throughout the brain during the course of Alzheimer’s disease leads to a decline in brain function.

Alzheimer’s disease is the most common form of dementia which affects over 90,000 people in Scotland.

Alzheimer’s disease attacks synapses and the loss of these synapse strongly predicts the reduced memory and cognitive abilities observed as the disease progresses.

In this study, researchers used powerful microscopy techniques to look at more than one million synapses from donated brain tissue of 42 people who had Alzheimer’s when they died to see the proteins existing in individual synapses. They found that smaller clumps of the protein, known as tau oligomers, remain in the synapses of people who died from Alzheimer’s disease.

Tangles of tau oligomers were discovered inside both sides of the synapse – from both the brain cell sending signals and the brain cell receiving signals.

Lead researcher, Professor Tara-Spires Jones of the UK Dementia Research Institute at the University of Edinburgh, 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.”

Investigating how they spread, researchers utilised a mouse model of the disease and discovered that the oligomers jumped from one side of the synapse to the other.

Evidence from these mouse models revealed that tau proteins spread from pre- to post synapse terminals in the brain and confirmed that the oligomeric tau is toxic to the synapses.

Researchers also found that, even without the presence of abundant large clumps of tau proteins – or tangles – the oligomeric tau is present.

The researchers suggest that the accumulation of the smaller clumps of tau proteins is an early event in the development of Alzheimer’s disease and targeted therapies to specifically reduce the oligomeric tau at synapses may slow its progression.

This article was contributed by the editorial team at healthandcare.scot