A13: A molecule that rejuvenates the brain?

The A13 antibody rejuvenates the brain by promoting the birth of new neurons and combating the defects that accompany the early stages of Alzheimer's disease. This opens up new possibilities for diagnosis and treatment.

An Italian study opens up new scenarios to combat Alzheimer's disease

The A13 antibody, developed at the EBRI (European Brain Research Institute), rejuvenates the brain by promoting the birth of new neurons and combating the defects that accompany the early stages of Alzheimer's disease. A strategy that opens up new possibilities for diagnosis and treatment. The study was published in the journal Cell Death and Differentiation.

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EBRI researchers found that neurogenesis in the adult brain is reduced at a very early stage of Alzheimer's disease. This alteration is caused by the accumulation in brain stem cells of highly toxic β-amyloid protein aggregates, called Aβ oligomers.

The team managed to neutralize the Aβ oligomers in the brain of an Alzheimer's disease mouse by introducing the A13 antibody into the brain stem cells, reactivating the birth of new neurons and rejuvenating the brain. In particular, researchers have shown how the strategy developed in the EBRI laboratories allows to re-establish the correct neurogenesis in the mouse model studied, recovering by 80% of the defects caused by the initial phase of Alzheimer's disease.

According to the authors, the importance of this research is twofold. On the one hand, it shows that the decrease in neurogenesis anticipates the typical pathological signs of Alzheimer's disease and could, therefore, help to detect the onset of the disease at a very early stage. On the other hand, it has been observed in vivo, in the mouse brain, the effectiveness of the A13 antibody in neutralizing Aβ oligomers right within neurons.

For the first time, in fact, the single "toxic bricks" that will form the extracellular β-amyloid plaques (the current therapeutic target of Alzheimer's disease) were intercepted and neutralized at their very start, before they cause irreversible neuronal damage.

This research, therefore, lays the foundations for the development of new strategies useful for the diagnosis and therapy of this neurodegenerative disease. For the research team, being able to monitor neurogenesis in the adult population will offer a potential diagnostic tool to signal the onset of Alzheimer's disease at a very early stage, i.e. when the disease is clinically pre-symptomatic. Moreover, the therapeutic use of the A13 antibody will allow neutralizing Aβ oligomers inside neurons, where they form for the first time, thus affecting the earliest possible event in the evolution of the disease.

The study was conducted on an animal model of Alzheimer's disease and gave very promising results and completely new evidence in the field. Nevertheless, the research is still in the preclinical stage.

1. Scopa C, Marrocco F, Latina V, Ruggeri F, Corvaglia V, La Regina F, Ammassari-Teule M, Middei S, Amadoro G, Meli G, Scardigli R, Cattaneo A. Impaired adult neurogenesis is an early event in Alzheimer's disease neurodegeneration, mediated by intracellular Aβ oligomers. Cell Death Differ. 2019 Oct 7. doi: 10.1038/s41418-019-0409-3.
2. European Brain Research Institute. Alzheimer: scoperta dai ricercatori dell’EBRI la molecola che ringiovanisce il cervello. https://www.ebri.it. 26/11/2019