Cystatin C can wash away Alzheimer's plaques

By Mike Nagle

- Last updated on GMT

Related tags Alzheimer's disease

Scientists have discovered that a protein called cystatin C can
prevent damaging Alzheimer's plaques from forming by keeping their
constituent protein water soluble.

Dr Efrat Levy, an associate professor at New York University, and his colleagues have conducted two studies in mice that show cystatin C, a cysteine protease inhibitor, binds to the soluble, non-pathological form of amyloid beta and so prevents the formation of the toxic plaques that are one of the hallmarks of Alzhiemer's.

"Given the increasing prevalence of this disease, its staggering social and economic costs for patients and their families, and the limitations of existing therapies, we are very hopeful that this research will lead to improved medications to prevent the disease and forestall its devastating symptoms," said Dr Harold Koplewicz, Director of the Nathan S. Kline Institute, where Levy also heads up a research lab.

The Alzheimer's Disease International estimates that there are 24m people worldwide who suffer from dementia and that over half of them have Alzheimer's.

Alarmingly, that figure is projected to rise to a staggering 81m by 2040.

Of the numerous Alzheimer's therapies in development, Levy plans to throw his hat into the ring and has already secured funding from the US Alzheimer's Association to begin the search for a drug that can mimic the effects of cystatin C.

In the first study, the scientists crossed two types of genetically modified mice so that they over produced both cystatin C and amyloid precursor protein (APP).

When the researchers removed the cystatin C using antibodies, they discovered that amyloid beta was also present in the mix, indicating the two proteins had bound to each other.

The end result was that there were less amyloid beta plaques formed in the brains of the mice.

"We are really excited by these findings because recent studies show that cystatin C is protective against a variety of insults that cause cell death in the brain.

Our potential therapeutic approach focuses on keeping amyloid beta in a water soluble form, preventing its accumulation in the brain, and thus slowing, halting, or reversing disease progression," said Levy.

Cystatin C is found in all bodily fluids and tissues of mammals and is connected to a large number of processes, including cell proliferation and growth, modulation of the inflammatory response, and bone resorption.

It has also been implicated in neuronal degeneration and repair of the nervous system.

The second study, run in collaboration with the laboratory of Dr Mathias Jucker at the Hertie-Institute for Clinical Brain Research in Tubingen, Germany, backed up these findings and confirmed that cystatin C has a direct effect on Alzheimer's rather a neuroprotective one.

The data also suggests that the interaction between the two proteins occurs outside of the cell and so could be more easily targeted by drugs.

However, Dr Levy explained that cystatin C production and body fluid levels vary among healthy individuals and can be influenced by certain hormones, ageing, and certain pathological conditions.

Indeed, a genetic variation in the cystatin C gene, namely the CST3 Thr25 allele, has been recently linked to lower levels of cystatin C and a greater risk of developing Alzheimer's disease.

The two studies were published in the online edition of Nature Genetics this week and will appear in the December print issue.

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