Alzheimer's Disease An Autoimmine Response?

Urgent Team

"I think it's time for us to start pushing the envelope and really exploring these new, radical ideas."

"[The] huge investment [on one basic approach] has been to our detriment. So I’d say I’m very hopeful and I think this is a potentially viable hypothesis."

"It is one of the only diseases that has had no therapeutic breakthroughs in over 16 years."

Saskia Sivananthan, neuroscientist, chief research officer, Alzheimer's Society of Canada

 

"There is definitely a black box in terms of what we should be considering as the next best approach. We need to think outside the box."

"Our immune system is a dynamic system; it's not like we're born with it and die with it. It is much more dynamic than our genetics and it is something we have not really capitalized on."

"I think that it [antibodies that mistakenly target the body’s own tissues — in the cerebrospinal fluid of Alzheimer’s patients] further fuels this original notion that autoimmunity could be centrally playing a role in the pathology of Alzheimer’s."

"For example, we have the observation that athletes that are prone to traumatic brain injuries, they have an increased incidence of Alzheimer’s disease. But in any case, any damage to the blood-brain barrier can actually open the door for these immune cells to enter into the brain tissue and further speed up the destruction of certain neuronal cells, which is central in the pathology of Alzheimer’s disease."

Ioannis Prassas, study co-author, scientist, Mount Sinai Hospital, Toronto

Daily Observer

The pharmaceutical industry has realized a 96.6 percent fail rate in its $3.5 billion investment over four years to 2020 in searching for a medical cure for Alzheimer's disease, according to a paper published in the International Journal of Alzheimer's Disease, last year. That's a spectacular investment and an equally spectacular failure on investment. 

The U.S. estimates that about four million of its citizens live with Alzheimer's disease. In Canada that number is about half a million people, although projections are that in coming years twice that number will be affected. The development of drugs for Alzheimer's treatment for the fatal ailment have come up with exactly no effective therapy to date. 

A new study out of Mount Sinai Hospital research laboratories in Toronto aims to change that situation, convinced that Alzheimer's is an autoimmune disease and the research that has been undertaken thus far has followed a different track altogether. The paper, published in the Journal of Applied Laboratory Medicine, examined the hypothesis that Alzheimer's may at least partially be an autoimmune disorder.

That the immune system is triggered by some foreign invader into the human body or an event within the body to cause the immune system to turn inward attacking healthy cells, according to the researchers who produced the study. A response that bears some resemblance to Type One diabetes onset, lupus disease or rheumatoid arthritis. 

 

With the use of sophisticated laboratory techniques of their own devising, the team found compelling evidence of several "autoantibodies" ... rogue products of the immune system responsible for such diseases ... that bind to brain-specific proteins, in Alzheimer's patients. 

Ioannis Prassas, one of the study's authors, described hallmarks of Alzheimer's being amyloid plaque and tangled 'tau' fibres forming on the brain which in time kill neurons. Focus has been almost entirely on attacking amyloid, in efforts to discover effective treatments, and they have failed, repeatedly. The Alzheimer's Society of Canada has chosen to direct its funding lately toward "High risk, high reward" projects in hopes of reaching a breakthrough on treatment of Alzheimer's.

Care of those with dementia comes with a high price tag, of $10.4 billion annually. Which might logically suggest that research funding from government should be geared toward reducing the human and financial cost related to the disease in an investment in novel ideas in achieving greater understanding of the cause of this terrifying body malfunction.

Clinical pathology professor Roger Bertholf of Weill Cornell Medical College, had an editorial published on the Canadian paper in the Journal of Applied Laboratory Medicine with a notation to the effect that evidence of a possible autoimmune role has been identified. Women over age 65, known to be more likely to develop autoimmune diseases, are also almost twice as likely to develop Alzheimer's than are men.

 

Some studies suggest use of anti-inflammatory painkillers have an effect on reducing the risk of Alzheimer's, a match to evidence of brain inflammation, as a product of immune responses in patients. The blood-brain barrier which normally blocks autoantibodies from affecting the brain is seen in Alzheimer's sufferers in whom that barrier has been compromised.

 

As a case in point, Dr. Prassas points out that athletes suffering serious brain injury can disrupt the barrier making them likelier to develop Alzheimer's. The Mount Sinai research team's working hypothesis is that the autoantibodies cause neuro-inflammation and trigger in some manner, death of neurons or destruction of the synapses connecting them.

 

Samples of cerebrospinal fluid taken from Alzheimer's and Parkinson's patients and otherwise healthy people with headaches, were studied by the team. Human brain tissue was mixed with antibodies extracted from the fluid, and a form of mass spectrometry was used to analyze the interaction. Strong evidence was found of autoantibodies targeting several brain proteins in the cerebrospinal fluid of Alzheimer's patients. None, however, discovered in the Parkinson's or the headache groups.

 

Eleftherios Diamandis, head of clinical biochemistry at University of Toronto, led the team and is now planning on a larger-scale study to attempt to confirm the initial findings with the hope that other scientists too, will adopt the concept and do their own confirmatory -- or not -- investigations. The researchers made note of the fact that the autoimmune process is identified increasingly in a number of diseases.

 

With the development of new technologym, doctors would be enabled to regularly monitor their patients' immune properties, offering personalized medicine to delay or to prevent diseases when troubling signs appear, theorized Dr.Prassas.

This photo provided by Mount Sinai Health System shows slices of human brains in the Mount Sinai Brain Bank that researchers are using to study Alzheimer's disease. (Mount Sinai Health System via AP)