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scientists unlock key to progression of alzheimer’s disease

experts used to think alzheimer's spread in the brain similarly to cancer.

by dave yasvinski

nov 1 2021

3 minute read

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scientists unlock key to progression of alzheimer’s disease

researchers at cambridge university made a breakthrough in understanding the progression of alzheimer's. (getty)

scientists using human data to track the progression of alzheimer’s over time have found the disease develops differently than initially thought — a discovery that opens the door to finding new ways to treat the world’s most common cause of dementia.

the research, published in the journal science advances , relied on a chemical kinetics approach developed at cambridge university combined with advances in precision pet scanning to gain new insights into a disease that has previously only been understood by studying animal models or the post-mortem brain samples of patients.

the team found that instead of developing in a single area of the brain and slowly causing the death of cells as it cascades outward, alzheimer’s disease is actually active in multiple areas of the brain simultaneously. progression is dictated by how quickly the disease kills nearby cells through the production of toxic protein clusters.

the two proteins implicated in the disease — tau and amyloid-beta — accumulate and form tangles that lead to the slow death of cells and a gradual shrinking of the brain. these tangles, or plaques (collectively referred to as aggregates), eventually lead to symptoms of memory loss, difficulty thinking or problem solving and changes in mood and behaviour.

by tracking tau proteins and applying five different datasets to the same mathematical model, the team discovered the progression of the disease was dictated by the replication of aggregates in individual regions of the brain and not the spread of aggregates between regions — a finding that runs contrary to the cascade theory of progression.

“the thinking had been that alzheimer’s develops in a way that’s similar to many cancers: the aggregates form in one region and then spread through the brain,” said georg meisl , first author of the study from cambridge’s yusuf hamied department of chemistry. “but instead, we found that when alzheimer’s starts there are already aggregates in multiple regions of the brain and so trying to stop the spread between regions will do little to slow the disease.”

they also discovered the spread of tau aggregates can take up to five years — much slower than initially thought. “neurons are surprisingly good at stopping aggregates from forming but we need to find ways to make them even better if we’re going to develop an effective treatment,” said sir david klenerman, the co-senior author of the study and a professor in the uk dementia research institute at the university of cambridge. “it’s fascinating how biology has evolved to stop the aggregation of proteins.”

there are over 500,000 canadians living with dementia today, with another 25,000 diagnosed with the progressive disease every year, according to the alzheimer society . two-thirds of those diagnosed over the age of 65 are women. at the rate at which the disease is growing, it costs over $12-billion a year to care for patients — an expense that underscores the importance of improving the ability to diagnose and treat the disease before it becomes too advanced for intervention.

“this research shows the value of working with human data instead of imperfect animal models,” said tuomas knowles, co-senior author of the study from the department of chemistry at cambridge. “it’s exciting to see the progress in this field — 15 years ago, the basic molecular mechanisms were determined for simple systems in a test tube by us and others; but now we’re able to study this process at the molecular level in real patients, which is an important step to one day developing treatments.”

the researchers are confident their methodology will not only assist in developing new treatments for the 44 million people suffering from alzheimer’s disease worldwide but help gain a better understanding of parkinson’s and other neurological diseases. they have already planned further study into the early development of alzheimer’s and other diseases related to the aggregation of tau proteins.

“the key discovery is that stopping the replication of aggregates rather than their propagation is going to be more effective at the stages of the disease that we studied,” knowles said.

dave yasvinski is a writer with  healthing.ca

dave yasvinski

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scientists unlock key to progression of alzheimer’s disease

experts used to think alzheimer's spread in the brain similarly to cancer.

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