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immunology

“It’s a chicken-egg situation,” said first author Dr Michael B Dinkins. “We don’t know if the anticeramide antibodies that may develop naturally during disease might be a result or a cause of the disease.” The scientists do know that excess ceramide in the brain results in the production of vesicles called exosomes, which start piling up around brain cells. What’s in them depends on which cell type makes them, but Dr Bieberich’s lab has evidence that when exosomes get taken up by other cells, they trigger cell death. The team thought this might be one way in which ceramide contributes to neurodegeneration in Alzheimer’s. “It takes a while before that becomes toxic because you have ongoing traffic and clearance mechanisms,” Dr Dinkins said. At some point, the clearance system stops working and toxic levels of amyloid and ceramide pile up. This led the team to adjust the ceramide levels downward by injecting even more ceramide under the skin, where it would mount an immune response and

Alzheimer’s may be an

autoimmune disease In a study published in the Journal of Alzheimer’s Disease, US neuroscientists have presented evidence suggesting the involvement of autoimmunity against the lipid ceramide in Alzheimer’s disease.

T

he leading hypothesis of Alzheimer’s is

that an accumulation of beta amyloid plaque first

ideally slow disease progression. “We thought we can immunise the mouse against its own ceramide - it develops antibodies, which neutralise the ceramide - and we get a similar effect as blocking its production, like a vaccination against it,” Dr Bieberich said. The method was expected to also block the subsequent chain of events that contribute to brain cell loss. But the team found elevated antibody levels already existed in their animal model and, when they added more ceramide, it not only increased antibody levels but also levels of plaque and exosomes. Female Alzheimer’s mice treated with more ceramide experienced about a 33% increase in amyloid formation, while their serum exosome levels increased 2.4 times. The finding has the team wondering if maybe exosomes, which can have a variety of functions including aiding communication, may be trying to intervene and that ceramide antibodies are blocking

team expected that generating antibodies against

their efforts. It also suggests that measuring blood

ceramide would hamper plaque formation.

levels of ceramide or some of its by-products

alters communication between brain cells, then

But the scientists found that the excessive

could be an early test for Alzheimer’s, since levels

prompts cell death. The new study’s corresponding

ceramide had already worked its way into the

were elevated well before mice showed signs of

author, Dr Erhard Bieberich, states that when inside

bloodstream, generating antibodies that supported

substantial plaque formation.

the brain, ceramide appears to increase beta amyloid

disease progression, particularly in female mice.

The team now aims to directly block ceramide

production, helping the plaque kill brain cells.

According to Dr Bieberich, this finding appears

using a genetically engineered mouse that from

Dr Bieberich’s lab, based at the Medical

to support the theory that Alzheimer’s is an

birth lacks the enzyme needed to make the lipid,

College of Georgia at Georgia Regents University,

autoimmune disease, which tends to be more

then crossbreeding it with an Alzheimer’s mouse

had previously identified elevated ceramide levels

common in women and is characterised by the

model. They hypothesise that the mice genetically

as a risk factor for Alzheimer’s and shown that

immune system producing antibodies against a

programmed to get Alzheimer’s will produce less

amyloid triggers excess production of the lipid. The

patient’s tissue.

ceramide, fewer exosomes and less plaque.

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