Wednesday, December 7, 2011

The liver could be the cause of Alzheimer's disease

Scientists from an American institute might just have revolutionized the treatment of Alzheimer's disease, a neurodegenerative disease that leads to loss of memory. While it was long thought that the underlying pathology starts somewhere in the brain, for an unknown reason, the researchers have shown that it actually seems to be the liver that induces the disease. If these findings can be verified, it is a revolution in our understanding of the disease, and it will have important implications for treatment, or finding a cure.

Experiments
In their experiments, the researchers used mice, and looked at how they developed a disease similar to Alzheimer's in humans. It was known from previous studies that a gene called Psen2 is important to develop the neurological pathology. Surprisingly, the scientists looked at the liver, rather than the brain, and found that unusual high expression of Psen2 is relevant to Alzheimer's when it is expressed highly in the liver, while high expression in the brain seemed less important. They showed that mice could inherit the disease when the gene was highly expressed in the liver, but this correlation was not found with overexpression in the brain.

β-amyloid
Psen2 is involved with incorrect folding of a protein dubbed β-amyloid, which causes them to stack and form plaques of protein that damage the brain in Alzheimer's. Why β-amyloid suddenly starts to fold in a bad way and form pathological accumulations is unknown, but the aformentioned study shows that the liver might be the cause of it. It seems that incorrect folding starts in the liver, and that they somehow end up in the brain, where it starts to become pathological. 


A new treatment
To test their hypothesis, the scientists treated mice with a drug that can not enter the brain. The drug, which is normally used for treating cancer patients, reduced the number of β-amyloid plaques found in the blood, but surprisingly also in the brain. This shows that the harmful proteins are able to travel up into the brain where they start wreaking havoc on neurons, that consequently become damaged. Neuronal damaged is characterized by the development of internal deposits called tangles by an abnormal form of yet another protein. The plaques and tangles are the two most defined characteristics of Alzheimer's. While the cancer drug further illustrates the liver origin of β-amyloid accumulation, it is of course also interesting to note that it can actually be treated. Regardless of the cause, using the anti-cancer drug could prove to be useful as a treatment while scientists work out the exact pathological mechanism of Alzheimer's.

Outlook
This study offers both a revolutionary new insight into Alzheimer's pathology, as well as a new therapy to treat the disease. If other studies validate the liver origin of pathological proteins, then we have a new target to develop a cure for Alzheimer's. Therapies that revolve around lowering the expression of Psen2 are a logical target. Because we previously had no clue where the plaques are coming from, it is hard to develop a targeted therapy. This study is an important step in the right direction.

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