Slowing Down The Development Of Alzheimer’s Plaques
Amyloid plaques are a hallmark feature in the brains of individuals suffering with Alzheimer’s disease. The problem is that once they’ve developed, it’s very difficult to reverse the process. This has made treatment of Alzheimer’s patients a particularly challenging hurdle. Now a group of scientists from the University of Michigan have managed to thwart one of the early processes contributing to plaque formation, thus slowing down their development in the lab.
Alzheimer’s disease is the most common form of dementia; dementia being an umbrella term for a group of different symptoms resulting from a decrease in brain function. Currently, over 800,000 people in the UK have dementia, two thirds of which are women. People with Alzheimer’s may experience an array of symptoms, depending on how advanced the disease is. Early stage symptoms may include forgetfulness and confusion in unfamiliar situations. Later down the line as the disease develops, patients may experience drastic personality changes, such as aggressiveness, severe short-term memory impairment and speech problems.
Alzheimer’s disease has two main causes within brain cells; the development of tangles of a protein called tau, and the accumulation of amyloid-beta proteins which form characteristic aggregates or plaques. These plaques and tangles cause death in brain cells such as neurons, and result in the large-scale degeneration of areas of the brain.
A team of researchers led by the University of Michigan Professor Yanzhuang Wang focused on amyloid-beta plaque formation. Aggregates of amyloid-beta are known to form when a protein called the amyloid precursor protein (APP) is chopped up whilst it is being transported inside the cell. The transport of this APP is regulated by a cellular structure called the Golgi. The Golgi acts like a cellular sorting office, packaging proteins before they are sent off to reach their correct cellular destination. It is also known that this Golgi becomes broken up, or fragmented, in nerve cells of Alzheimer’s patients. This causes an increase in the transport, or secretion, of the APP protein, and therefore enhances the production of amyloid-beta proteins. How exactly this occurred was unknown prior to this study.
In a study published in PNAS, the scientists found that amyloid-beta accumulation causes the activation of a particular protein called cdk5; this triggered the Golgi to fragment. By inhibiting this protein, the team managed to rescue this Golgi structure, which in-turn reduced amyloid-beta secretion by approximately 80 percent.
Although these results are promising, we must tread carefully when extrapolating information from laboratory based studies. The next important stage is to see if the same effect can be achieved in animal models; Wang is hoping to investigate this through a collaborative project with researchers from the U-M Health System and U-M Molecular and Behavioral Neuroscience Institute. Eventually, it is possible that these findings could be applied to the prevention of plaque formation in humans, but we are a long way off yet.