Alzheimer’s: cerebral fluid, key actor in the aggregation of toxic proteins

Alzheimer’s: cerebral fluid, key actor in the aggregation of toxic proteins


The brain contains several distinct fluids, including the interstitial cerebral fluid in which the nerve cells bathe. This liquid ensures the transport of nutrients, ions and neurotransmitters essential to neural activity, but also the elimination of waste. The mechanisms underlying this elimination are still misunderstood and constitute a subject of active debate. In particular, the role of this interstitial fluid in the accumulation of amyloid proteins, these aggregates characteristic of the appearance and progression of Alzheimer’s disease, remains practically unknown.

A team from the theoretical biochemistry laboratory (CNRS/University Paris Cité), in collaboration with Italian scientists, has undertaken to model this fluid and simulate the movement of individual or aggregated amyloid proteins. Thanks to advanced digital simulations, based on the combination of fluid dynamics and molecular dynamics techniques, they were able to precisely describe the displacement of amyloid proteins in this fluid environment. They have shown that, unlike certain previous hypotheses, diffusion is the main mechanism allowing small proteins to move and be eliminated. On the other hand, when these proteins start to assemble in broader structures, they are potentially driven by the movement of the fluid, which could accelerate their accumulation.

The study also reveals that local hydrodynamics – the currents and constraints exerted by the fluid on proteins – promotes the aggregation of amyloid proteins at each stage of their formation. This phenomenon could explain why certain areas of the brain are more affected by the disease. Finally, the presence of aggregates modifies the circulation of fluid, creating a vicious circle where toxic clusters continue to develop.

These discoveries, published in PNAS NEXUSopen promising prospects for the development of new therapies against Alzheimer’s disease. By better understanding the role of the cerebral interstitial fluid in the aggregation of proteins, scientists could identify strategies to improve the elimination of toxins or design treatments directly targeting these fluid dynamics.

Writer: Apr

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