Enzyme breaks down Alzheimer's plaque component

By Wai Lang Chu

- Last updated on GMT

Related tags Alzheimer Alzheimer's disease

Scientists have uncovered a naturally occurring enzyme that can
break down a component of the brain plaques that play a central
role in Alzheimer's disease, which could provide researchers with a
basis for new therapies to treat this disorder.

Alzheimer's disease is the most common cause of dementia, accounting for about 60 per cent of all cases. It's a progressive disease of the brain that causes dementia, gradually destroying a person's memory and ability to learn, reason, make judgements, communicate and carry out normal daily activities.

Current drugs to treat this disorder, donepezil, rivastigmine and galantamine, are of some value in certain people with early Alzheimer's disease. Patients only continue this treatment only if the person improves or at least does not become worse, and people must be reviewed every six months.

Medical researchers are currently investigating other medical treatments, including anti-oxidants, brain stem cell therapy and a vaccination to stop the build up of plaques in the brain (a hallmark of Alzheimer's disease).

In this latest piece of research researchers at Washington University School of Medicine in St. Louis showed that the enzyme, matrix metalloproteinase 9 (MMP-9), degrades abnormally aggregated proteins known as amyloid fibrils, a main ingredient of brain plaques. In the brain, support cells known as astrocytes make MMP-9.

MMP-9 has already been linked to cancer metastases, vascular disease, arthritis and arthritis and establishing a direct Alzheimer's link is encouraging as previously identified enzymes only degrade a smaller, nonaggregated component of Alzheimer's plaques.

The study, led by Jin-Moo Lee, assistant professor of neurology found that disabling the mouse gene for MMP-9 increased levels of amyloid beta (Abeta) in the spaces between brain cells.

The finding proves that MMP-9 contributes to clearance of Abeta from extracellular spaces and suggests its dysfunction could potentially contribute to the development of Alzheimer's.

"We already knew of three enzymes that break down amyloid beta (Abeta), a protein fragment that clumps together with itself to form the fibrils,"​ said Lee, "But the thinking up until now had been that Abeta might be clumping together so tightly that the fibrils were indestructible."

"MMP-9 and other enzymes like it are secreted from brain support cells and active in the spaces outside of cells, and that's where we saw an increase in Abeta levels in the mice that lacked the gene for MMP-9. That's relevant to Alzheimer's because all the amyloid plaques are extracellular, and the formation of the plaques seems to be related to an elevated level of Abeta that accumulates over time in those spaces."

It is not known exactly what causes Alzheimer's disease. Scientists think there is unlikely to be a single cause, but a number of factors that come together to trigger the disease.

Age is the greatest risk factor for Alzheimer's disease, with most cases affecting people over 65. The likelihood of developing the disease doubles every 5 years after age 65.

Family history of the disease is a risk factor, and the risk of developing the disease is higher if a parent, sister or brother has it.

Scientists have found some genes that are known to directly cause Alzheimer's, so that anyone who inherits them is almost certain to develop the disease, usually before age 65, and sometimes as early as their 30s or 40s.

However, these genes have been found in only a few hundred families worldwide. Alzheimer's caused by these genes is known as 'familial Alzheimer's disease'.

Related topics Preclinical Research

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