Scientists Identify the Cause of Alzheimer’s Progression in the Brain – Very Different Than Previously Thought

Brain Scan Concept Animation

In Alzheimer’s disease, the buildup of tau and amyloid-beta proteins forms tangles and plaques, known as aggregates, leading to brain cell death and shrinkage. Researchers found that the progression rate in Alzheimer’s disease is controlled by aggregate replication within individual brain regions, not their spread between regions.

For the first time, researchers have used human data to quantify the speed of different processes that lead to Alzheimer’s disease and found that it develops in a very different way than previously thought. Their results could have important implications for the development of potential treatments.

The international team, led by the University of Cambridge, found that instead of starting from a single point in the brain and initiating a chain reaction that leads to the death of brain cells, Alzheimer’s disease reaches different regions of the brain early. How quickly the disease kills cells in these regions, through the production of toxic protein clusters, limits how quickly the disease progresses overall.

The researchers used post-mortem brain samples from Alzheimer’s patients, as well as PET scans from living patients, who ranged from those with mild cognitive impairment to those with late-stage Alzheimer’s disease, to track the aggregation of tau, one of two key proteins implicated in the condition.

“This research shows the value of working with human data instead of imperfect animal models.” — Tuomas Knowles

In Alzheimer’s disease, tau and another protein called amyloid-beta build up into tangles and plaques – known collectively as aggregates – causing brain cells to die and the brain to shrink. This results in memory loss, personality changes, and difficulty carrying out daily functions.

By combining five different datasets and applying them to the same mathematical model, the researchers observed that the mechanism controlling the rate of progression in Alzheimer’s disease is the replication of aggregates in individual regions of the brain, and not the spread of aggregates from one region to another.

The results, reported in the journal Science Advances, open up new ways of understanding the progress of Alzheimer’s and other neurodegenerative diseases, and new ways that future treatments might be developed.

For many years, the processes within the brain which result in Alzheimer’s disease have been described using terms like ‘cascade’ and ‘chain reaction’. It is a difficult disease to study, since it develops over decades, and a definitive diagnosis can only be given after examining samples of brain tissue after death.

For years, researchers have relied largely on animal models to study the disease. Results from mice suggested that Alzheimer’s disease spreads quickly, as the toxic protein clusters colonize different parts of the brain.

“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 Dr. Georg Meisl from Cambridge’s Yusuf Hamied Department of Chemistry, the paper’s first author. “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.”

This is the first time that human data has been used to track which processes control the development of Alzheimer’s disease over time. It was made possible in part by the chemical kinetics approach developed at Cambridge over the last decade which allows the processes of aggregation and spread in the brain to be modeled, as well as advances in PET scanning and improvements in the sensitivity of other brain measurements.

“This research shows the value of working with human data instead of imperfect animal models,” said co-senior author Professor Tuomas Knowles, also from the Department of Chemistry. “It’s exciting to see the progress in this field – fifteen 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 found that the replication of tau aggregates is surprisingly slow – taking up to five years. “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 co-senior author Professor Sir David Klenerman, from the UK Dementia Research Institute at the University of Cambridge. “It’s fascinating how biology has evolved to stop the aggregation of proteins.”

The researchers say their methodology could be used to help the development of treatments for Alzheimer’s disease, which affects an estimated 44 million people worldwide, by targeting the most important processes that occur when humans develop the disease. In addition, the methodology could be applied to other neurodegenerative diseases, such as Parkinson’s disease.  

“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,” said Knowles.

The researchers are now planning to look at the earlier processes in the development of the disease, and extend the studies to other diseases such as Frontal temporal dementia, traumatic brain injury, and progressive supranuclear palsy where tau aggregates are also formed during disease.

Reference: “In vivo rate-determining steps of tau seed accumulation in Alzheimer’s disease” by Georg Meisl, Eric Hidari, Kieren Allinson, Timothy Rittman, Sarah L. DeVos, Justin S. Sanchez, Catherine K. Xu, Karen E. Duff, Keith A. Johnson, James B. Rowe, Bradley T. Hyman, Tuomas P. J. Knowles and David Klenerman, 29 October 2021, Science Advances.
DOI: 10.1126/sciadv.abh1448

The study is a collaboration between researchers at the UK Dementia Research Institute, the University of Cambridge, and Harvard Medical School. Funding is acknowledged from Sidney Sussex College Cambridge, the European Research Council, the Royal Society, JPB Foundation, the Rainwater Foundation, the NIH, and the NIHR Cambridge Biomedical Research Centre which supports the Cambridge Brain Bank.

28 Comments on "Scientists Identify the Cause of Alzheimer’s Progression in the Brain – Very Different Than Previously Thought"

  1. The bitch products are labeling illegal DNA scams as ALZHEIMER. Where are the nukes ?

  2. Argle bargle!

  3. Sounds a lot like toxic spike proteins, generated by cells, that cause brain fog, strokes, seizures. Long term issues are unknown. Now they’re jabbing children.

  4. Do plant eaters who exercise regularly to better?

  5. J Slade knows the ways to prevent ailments and promote longevity.

  6. Make sure you are getting your rock salts!

  7. Is it just me, or do most of the above comments make absolutely no sense?

  8. My grandmother is 87 she has alz/ dementia. I believe it is from years of isolation. I live in Maryland she in Mississippi. When I lived in Florida, I saw her more often and the rest of the family. After moving back to Maryland in 2006, the remaining family down south stopped visiting her except on holidays. I think loneliness and isolation definitely speed up the progression of the disease.

  9. If I may be allowed to comment about this disease; Yes, I had witnessed it from my “father-ln-Law…; once it start, it distributes to all part of their body gradually. Then, they started not to know where they are,or of time, day, or going to the simple bath-room.
    I think the disease is like “Amoeba” studied in biology that keeps breaking up and multiplies and duplicating itself.
    To cure this type of disease you will have to identied it at early stage or knowing what are the characteristic of the “Gen” combinations that makes it to be “Alheimer” then, you can find the medicines to follow this immutations wherever they go in parts of the patients, because they distribes all over the body, but found inside the brain as a better place to live in.
    I am not a doctor, but scientist.
    That is my thought.

  10. Everyone in this thread, save for “Huh?”, is a complete f*cking ret*rd, and make me shudder when I contemplate our collective future.

  11. I am not a doctor or a scientist but I have been involved in both disciplines for decades it appears that Alzheimer’s it’s just a blanket term for different parasitic diseases Mercury toxicity lead toxicity and anything else that can burn off the the myelin sheath of the nerves

  12. Cynthia Welborn | November 1, 2021 at 7:42 pm | Reply

    This is a thought of mine, my mother at one point suffered from a bad case of shingles all over her head & back of neck. After this illness is when she started having dementia/Alzheimer’s & rapidly & progressively got worse?! My mother-in-law also suffered from the exact same thing & also developed this horrible disease. The shingles caused the nerve damage that onset Alzheimer’s! I’m sure that not all that die from disease get shingles but it was what caused the nerve damage that led to the disease for them & led to their dying from Alzheimer’s Js what destroys the nerves destroy the brain…

  13. Jadean U England | November 2, 2021 at 2:43 am | Reply

    I almost felt like I wasted 90 seconds of my precious life reading all your brain farts until Welborn’s comment. I believe she is on to something right there. Great Observations Lil Ms.

  14. It really frustrates me that such clever people as these researchers, haven’t figured out yet that there’s a direct link between Alzheimer’s, cancer, inflammation and diet. They are trying to solve a self inflicted problem by developing a “cure” for the symptoms. That’s not a cure. The cure I’d to eat less processed foods, yo use less fat in meals and cut down on meat. It should be rather obvious, that tribespeople don’t get Alzheimer’s, and animals don’t either. So why do we humans get Alzheimer’s and cancer? Why do only our pets out of all other animals get cancer? Diet.

  15. ? Looks like some commenting here suffer from the disease. Just a thought ……

  16. My Parents moved from South Florida Miami to North Florida after hurricane Andrew distoryed their home of plus 30 years. They were in their late 60s why here in the middle of nowhere. By 10 years later my mom had a brain 7 cm tumor every the same after that by 10 years later my mom developed dementia 3 years . I took a leave of absence from work to take care of my mom from September to April 7th she passed away. I could see the progression of the dementia. During this time I stated see the Alzheimers starting in dad first sign was him getting up from a nap he would say it morning whats for breakfast then between 4p and 5p start seeing people down at the river are nurse called it sundowners.

  17. Verands sdnarev | November 2, 2021 at 8:26 am | Reply

    Intermitant fasting is already starting to reverse the effects of alz/dimen in many naturalistic case studies.

    There is a joe rogan who has a leading nutritionist/physiologist who is pioneering age/disease reversing processes using intermitant fasting.. All your immune system lives in the gut… Give it the digesting break it needs.

  18. I wonder if the recently discovered lymph nodes in the brain are part of this story. If they are working and robust, perhaps they participate in clearing the tau, and if not, perhaps that is a cause of buildup. Since the presence of these nodes is recent, 3-4 years, it may not have been considered in experimental design to date.

  19. ISRIB anyone?
    It is not a drug, it is a chemical, too small a molecule and way too inexpensive to be a drug.
    Seems to reverse age related cognitive impairment in lab animals – like overnight.
    Seems to reverse cognitive deficits in lab animals with Trisomy 21 / Down Syndrome – like overnight.
    Seems to reverse TBI, traumatic brain injury, in lab animals – like overnight.
    Somehow – like overnight – Google / Alphabet / Calico saw the promise and licensed it. And pretty much silence has followed. I guess we are looking for a way to get the price of a treatment up from $200 to around $30000? LOL, just sayin.
    I am interested in it, know someone dear to me who might have his life back from a treatment with it, but I hear nothing about this chemical. Check it out and ask your primary care physicians why there is only silence on this.

  20. But this article said they “identified the cause of Alzheimer’s progression”; Why didn’t the article tell us what they identified?

    It also said “when Alzheimer’s starts there are already aggregates in multiple regions of the brain”

    So it starts before it starts then, right? Got it!

  21. Aggregates form. Seems like a plaque like build up that eventually over comes the neurons and prevent communication between the different regions of the brain. The collective data may point out either one how to boost the neurons ability to clear the build up by providing either the building blocks of the process whether that is through nutrients or through regular use to keep the pathways used. Two a means of identifying the electron level of attraction that cause the aggregates to form. Every biological cell I have ever read on has some level of electrical activity and biological process to take in nutrients and expel waste. What process generates these aggregates? I thank the research teams and all the financial supporters having loved ones diagnosed with the disease. It is well beyond my level; however, all breakthroughs are encouraging.

  22. Conference Series LLC Ltd invites worldwide global audience and presenters to participate at the Worldwide Forum on Alzheimer and Dementia which is to be held in New York, USA during June 21-22, 2022. Special interest and theme of the conference is “Future of Dementia & Alzheimer: Innovations and Research ”. This event will cover prompt keynote presentations, Oral talks, Poster and presentations. Dementia 2022 aims to sharing new ideas and technologies amongst the professionals, industrialists, and students from research areas of Psychology, academic scientists, professors, and Research.

  23. Cambridge researchers’ new findings on the spread of Alzheimer’s in the brain correlate with our treatment modalities. With EEG biofeedback, positive results are obtained in the treatment of Alzheimer’s patients by creating changes in many parts of their brains.

  24. DJB3 Action said so | November 10, 2021 at 5:08 pm | Reply

    Connect the dots.Work all the “knowns” to establish understanding the rest.Create positive new neurological pathways by always challenging the brains capabilities.

  25. My grandmother had alzheimers. People born in the early 1900s had no idea about pollution, diet, or heavy metals. Her well water used to come out red with rust and she drank it everyday, saying, oh just let it run a minute. They had lead paint too.. I fully believe heavy metals play a part. As people become more educated about water quality and diet I think the disease will become less common. Just remember, everytime you get a cat scan, gadolinium deposits in your brain.

  26. Jennifer Robbins | November 10, 2021 at 6:32 pm | Reply

    Wellborn is right on! My grandmother had shingles and Alzheimer’s progressed after.

  27. Many of these comments sound like they come from people already in the latter stages of Alzheimers. Please find a cure for them asap!

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