(CN) — A research team led by scientists at the University of Cambridge used human data to determine how Alzheimer’s disease develops in the brain.
The research, published in the journal Science Advances on Friday, used post-mortem brain samples from Alzheimer’s patients and PET scans from living patients to track how a key protein called tau aggregates and worsens the symptoms of the neurodegenerative disease. The findings indicate the disease develops in multiple different regions of the brain early, rather than starting from a single point and spreading from one region to another.
Paul Rosenberg, professor of psychiatry and behavioral sciences and co-director of the Memory and Alzheimer’s Treatment Center at Johns Hopkins Medicine, said the study was “pretty persuasive” and while the results might not be “stunning,” they could be helpful in treatment development.
“They asked the question, ‘How does tau spread through the brain? Does it actually spread, or does it just start in different places in a predictable pattern?’ And their answer was the latter,” Rosenberg said. “It’s being deposited in different parts of the brain. It’s a predictable pattern and predictable order of deposition, but it’s not spreading. It’s not going from one place to another.”
Rosenberg said that the study does not present a way to treat or cure Alzheimer’s, but it does help explain why other treatments are not working.
Alzheimer’s disease and the associated memory loss, personality changes and difficulties with daily functions are believed to be the result of tau and another protein called amyloid-beta building up into tangles and plaques. These tangles and plaques cause the brain to shrink and brain cells to die.
Rosenberg said that for the past few decades, Alzheimer’s treatments focused on eliminating the amyloid protein.
“We finally have drugs that are effective in removing amyloid, and their effect is either none or modest. They don't look like they're going to really blow us away in terms of helping our patients very much,” Rosenberg said. He highlighted that while amyloid is overwhelmingly present in people with Alzheimer’s, the cognitive impairments associated with the disease do not come until the brain deposits tau.
Consequently, some researchers have pivoted to treatments that eliminate tau. The problem is that tau is difficult to target — it’s located within the brain neurons and it plays an important role in some physiological functions. Rosenberg said this raises questions of how and when to go after tau.
Some treatments have attempted to use antibodies to remove the tau, or at least prevent it from spreading throughout the brain. Rosenberg said these antibody treatments have largely faltered, and this study may demonstrate why.
“People were thinking that it spread neuron to neuron. This series of studies goes against that,” Rosenberg. “It tells you that the antibodies might not work.”
In a statement announcing the study’s findings, the researchers echoed Rosenberg’s explanation.
“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,” said Georg Meisl, one of the Cambridge scientists and the paper’s first listed author.
According to the statement, the study is the first to collect data from humans rather than animals to monitor the disease’s progression over time.
“This research shows the value of working with human data instead of imperfect animal models,” said Tuomas Knowles, a professor of physical chemistry and biophysics at Cambridge and co-senior author of the study. “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 said in the statement that they are now planning to examine earlier processes in the development of Alzheimer’s disease. They said they also plan to study other tau diseases, like frontal temporal dementia, traumatic brain injuries and progressive supranuclear palsy.
While scientists hunt for effective treatments, Rosenberg said he fosters hope in his patients by encouraging them to lead a healthy lifestyle. He said there is “mounting evidence” that things like aerobic exercise, proper sleep, making time for leisure and socialization, wearing hearing aids if needed, managing stress, and following a heart-healthy diet could help prevent cognitive decline.
“In general, what’s good for the heart is good for the head,” Rosenberg said. “We haven't proven it in a [clinical] trial, but if we estimate the effect, it's as large as any drug that we're ever going to see. I think if you lead a healthy lifestyle, you can slow it down considerably.”
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