New research on protein clumping in the brain reveals how brain cells can still function properly. This opens the door to new therapies for conditions like Alzheimer's and frontotemporal dementia.
A team of researchers from Vrije Universiteit Amsterdam and Amsterdam UMC has specifically focused on the protein tau. "Tau clumping is a key factor in the loss of brain cells in Alzheimer's disease and frontotemporal dementia," neuroscientist Wiep Scheper explains. "Tau clumping reduces the ability of brain cells to produce new proteins. Proteins are the cell's workhorses, and if brain cells can't produce enough new proteins, they can't properly perform their functions, such as memory formation, and they eventually die."
Waste factories are of great value
Over a century ago, researchers discovered that in the brains of people with Alzheimer's disease, some brain cells with tau protein accumulations also contained granulovacuolar degeneration vesicles (GVBs). GVBs are a type of lysosome, the cell's waste factories. At the time, it was unclear what the presence of GVBs meant for the brain cells. Scheper's laboratory has discovered that brain cells with GVBs can resist the toxic effects of tau clumps on protein synthesis and cell death. This research has been published in the leading journal Science Advances.
This resilience, which is stimulated in brain cells with GVBs, is already naturally present in our brain cells. By further stimulating this process, brain cells with tau clumps can continue to function better. This research demonstrates new opportunities for developing treatments for brain diseases in which tau accumulates, such as Alzheimer's disease and frontotemporal dementia.
New protein production is possible despite tau clumps
Neuroscientist Jasper Smits, along with a team of researchers from Amsterdam UMC and Vrije Universiteit Amsterdam, has mapped several key components of the underlying molecular mechanism. Crucially, nerve cells with GVBs, despite the presence of tau clumps, can still produce new proteins when they become active. This is essential for processes such as proper memory function. This demonstrates that the resilience associated with GVBs is crucial for maintaining proper brain cell function.
This resilience, which is stimulated in brain cells with GVBs, is already present in our brain cells. By further stimulating this process, brain cells with tau clumps can continue to function better. This research demonstrates new opportunities for developing treatments for brain diseases in which tau accumulates, such as Alzheimer's disease and frontotemporal dementia.
The study was made possible by funding from the Hersenstichting (Netherlands Brain Foundation)/Coby van Nieuwkerk Fund and the Dutch Research Council (NWO).