Canadian study fuels theory Alzheimer's an auto-immune disorder

Using sophisticated lab techniques, the team found strong evidence in Alzheimer’s sufferers of several 'autoantibodies' that bind to brain-specific proteins

Tom Blackwell, National Post 4 minute read May 14, 2021

Amid the COVID-19 emergency, it has been easy to forget another looming health crisis.

Unchecked by lockdowns or masks, Alzheimer’s disease still afflicts half a million Canadians and is projected to sicken almost twice that many in coming years. And despite numerous attempts at developing drugs to treat the always-fatal ailment, no effective therapy has emerged.

But a new Canadian study hints at a novel and largely overlooked hypothesis, one that could open up a whole new avenue of pharmaceutical attack if borne out.

Alzheimer’s may be at least in part an autoimmune disorder, an illness like rheumatoid arthritis or lupus triggered by patients’ immune systems turning inward and attacking healthy cells, argue researchers at Toronto’s Mount Sinai hospital.

Using sophisticated laboratory techniques they developed, the team found strong evidence in Alzheimer’s sufferers of several “autoantibodies” — rogue products of the immune system responsible for such diseases — that bind to brain-specific proteins.

It’s early-stage work and needs to be replicated on a larger scale. But given the state of Alzheimer’s science today, such ideas must be pursued, argues Ioannis Prassas, a Mount Sinai scientist and one of the study’s authors.

The hallmarks of the disease are amyloid plaque and tangled “tau” fibres that form on the brain, eventually killing off neurons. Attempts to find treatments have focused almost exclusively on attacking amyloid, and have repeatedly failed, Prassas noted.

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

The study’s results are “very interesting” and the auto-immune hypothesis a plausible one that deserves more attention and funding, said neuroscientist Saskia Sivananthan, chief research officer for the Alzheimer’s Society of Canada.

In fact, the society has changed its approach to funding dementia science in the last two years, directing more dollars to new ideas — “high risk, high reward” projects that might provide a much-needed breakthrough, she said.

“I think it’s time for us to start pushing the envelope and really exploring these new, radical ideas,” said Sivananthan.

The “huge investment” on one basic approach, she said, “has been to our detriment.”

It’s a pressing concern, with dementia already costing health care, and the economy more broadly, $10.4 billion annually.

But Sivananthan said attempts to break new ground are hampered in Canada by government funding of dementia research that lags well behind other G7 countries. In 2016, for instance, Canada committed barely a fifth of what the U.K. did, says the Alzheimer’s Society.

The search for a treatment worldwide has certainly been gloomy.

The pharmaceutical industry spent $3.5 billion on it over the four years up to 2020 — with a 96.6 per cent failure rate, according to a paper last year in the International Journal of Alzheimer’s disease.

Meanwhile, there’s already evidence of a possible autoimmune role in Alzheimer’s, notes Roger Bertholf, a clinical pathology professor at Weill Cornell Medical College, in an editorial on the Canadian paper in the Journal of Applied Laboratory Medicine.

Women over 65 are almost twice as likely to develop Alzheimer’s, and also much more likely to develop known autoimmune diseases. There is evidence of brain inflammation — a product of immune responses — in patients, and some studies suggest that use of anti-inflammatory painkillers reduces the risk of Alzheimer’s.

A compromised blood-brain barrier, which would normally block those autoantibodies from affecting the organ, is seen in Alzheimer’s sufferers. Indeed, athletes suffering from serious brain injury, which can disrupt the barrier, are more likely to develop the disease, said Prassas.

The Toronto team’s hypothesis is that the autoantibodies cause neuro-inflammation and somehow trigger death of neurons or destruction of the synapses that connect them.

They looked at samples of cerebrospinal fluid from Alzheimer’s and Parkinson’s patients and otherwise healthy people with headaches.

In simple terms, they essentially mixed human brain tissue with antibodies extracted from that fluid and used a form of mass spectrometry to analyze the interaction.

They found strong evidence of autoantibodies targeting several brain proteins in the cerebrospinal fluid of Alzheimer’s patients, but none in the Parkinson’s or headache groups.

The team — led by Eleftherios Diamandis, the University of Toronto’s head of clinical biochemistry, and including student Bryant Lim — is now planning a larger-scale study to try to confirm their findings, and hope other scientists pursue the concept.

They also note the auto-immune process is being identified in an increasing number of diseases, and imagine an intriguing future related to that. New technology could let doctors regularly monitor patients’ immune properties, Prassas said, and offer personalized medicine to delay or prevent diseases when trouble signs appear.

“Our immune system is a dynamic system; it’s not like we’re born with it and die with it,” he said. “It is much more dynamic than our genetics and it is something we have not really capitalized on.”


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