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Landmark discovery in the fight against Alzheimer's

By John von Radowitz

A major discovery linking Alzheimer's to a natural process that "prunes" nerve connections in the brain has raised hopes of stopping the disease in its tracks.

Scientists demonstrated the mechanism in mice engineered to suffer Alzheimer's-like symptoms, and used an antibody to block it.

A human version of the same molecule is currently being developed by a US biotech company.

The researchers showed how neural connections, or synapses, are lost in the earliest stages of Alzheimer's, before symptoms appear or tell-tale protein fragment "plaques" accumulate in the brain.

They found that, ironically, what lies behind this destructive effect is a vital component of normal brain development during infancy and childhood.

As the young brain develops, excess synapses have to be "pruned" to keep neural circuitry in order. Defensive cells called microglia "eat" the synapses, guided by so-called "complement" proteins that assist the immune system.

The US team found that the same pruning mechanism, operating inappropriately, was responsible for early synapse loss in Alzheimer's disease.

Central to the process was a particular complement protein called C1q. When the C1q signalling pathway was blocked, synapse loss in the mice was halted.

A human form of the C1q-blocking antibody is now at an early stage of development at Annexon Biosciences, a biotech company based in San Francisco.

Belfast Telegraph


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