When the accumulations of the protein destroy the synapses, the neurons produce new quantities of this substance, and the massacre is perpetuated: the infinite “loop” could partly explain why many pharmacological trials for this form of dementia do not work.

A group of British researchers studying the degenerative mechanisms characteristic of Alzheimer’s disease has observed a “vicious circle” in the accumulation of beta-amyloid protein, which could partly explain why many trials of drugs in charge of counteracting it have so far proved ineffective.

One of the recurrent traits in the brain affected by Alzheimer‘s is the accumulation of beta-amyloid protein plaques, disordered piles of a metabolic waste substance that surround and destroy the synapses, the nerve centers of communication between neurons. This process leads to cell death, brain atrophy and cognitive problems, including memory loss.

The nature of beta-amyloid and its role in the origin of the disease are not entirely clear: we are still asked, for example, whether it is the cause or symptom of this form of dementia; other studies attribute a protective role on neurons before uncontrolled proliferation.

In the new study, published in Translational Psychiatry, researchers found that when beta-amyloid aggregations destroy a synapse, nerve cells produce new amounts of the protein in response, thus putting new synapses at risk.

“We show that there is a vicious circle in which beta-amyloid stimulates its own production,” explains Richard Killick of the Institute of Psychiatry, Psychology & Neuroscience at King’s College London. “We believe that when this loop gets out of control it’s too late for drugs targeting beta-amyloid to be effective. This could explain why so many drug trials against Alzheimer’s have failed. ”

ADJUST THE OBSTACLE. Among the main actors in this vicious circle is a protein well known to those who study Alzheimer’s disease: it is called Dkk1 and is a powerful stimulator of beta-amyloid production. Its concentration in the brain increases with age. According to the researchers, this protein could be a better pharmaceutical target than true amyloid plaques. Targeting it could help undermine the newly identified continuous mechanism of toxic protein production.

Hülya Karahan: The Faunder

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