Liver protein could protect against Alzheimer’s

A PROTEIN found in the liver may protect against Alzheimer’s disease by stopping the build-up of plaque, a new study found.

Fans in old Falkirk strips, to raise awareness for Alzheimer Scotland. Picture: JP
Fans in old Falkirk strips, to raise awareness for Alzheimer Scotland. Picture: JP

The protein, which tends to form harmful aggregates when it is produced in the liver, appears to protect against Alzheimer’s disease when it is produced in the brain.

Groups, or aggregates, of amyloid beta proteins develop in the brains of people with Alzheimer’s disease. These form “amyloid plaques” which are thought to contribute to the nerve cell death that causes Alzheimer’s symptoms.

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Professor Joel Buxbaum of The Scripps Research Institute in Florida said: “This result was completely unexpected when we started this research.

“But now we realise that it could indicate a new approach for Alzheimer’s prevention and therapy.”

The finding published in the Journal of Neuroscience focused on transthyretin (TTR), a protein known to function as a transporter, carrying the thyroid hormone thyroxine and vitamin A through the bloodstream and cerebrospinal fluid.

To do this it must come together in a four sub-unit structure called a tetramer.

Certain factors such as old age and TTR gene mutations can make these tetramers prone to fall apart and misfold into tough aggregates called amyloids.

TTR amyloids accumulate in the heart, kidneys, peripheral nerves and other tissues and cause life-shortening diseases including familial amyloid polyneuropathy and senile systemic (cardiac) amyloidosis.

Dr Buxbaum built on previous research that hinted that TTR in the brain might protect against other amyloids – particularly the Alzheimer’s associated protein amyloid beta.

Lab experiments showed TTR seemed able to grab hold of amyloid beta and prevent it from aggregating. Mice overproduced amyloid beta and TTR expression was increased in affected brain tissue providing a protective affect.

Scientists analysed a segment of DNA near the TTR gene called the promoter region, where special DNA-binding proteins called transcription factors could increase TTR gene activity.

The analysis suggested that Heat Shock Factor 1 (HSF1), known as a master switch for a broad protective response against certain types of cellular stress, could bind to the TTR gene’s promoter.

Researchers found that in liver cells the HSF1 response somehow brought about a modest decrease in TTR production.

In liver cells TTR activity rose when HSF1 was blocked, suggesting that HSF1 helps keep a lid on liver TTR production.

Dr Buxbaum added: “It’s becoming evident that the same molecule can do very different things in different contexts.”

The next stage is to develop a small molecule compound, suitable for delivery in a pill, that at least modestly boosts HSF1 activity and/or TTR production in neurons – and thus might prevent or delay Alzheimer’s dementia