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posted by requerdanos on Saturday August 21 2021, @09:40PM   Printer-friendly
from the please-let-this-be-it-this-time dept.

Alzheimer's discovery reveals "Achilles' heel" of synapse degeneration:

Scientists believe one of the key culprits behind the cognitive decline seen in Alzheimer's are amyloid beta proteins that clump together and disrupt the brain's synaptic connections, but how they carry out such degeneration has remained unclear. A new study has shone compelling new light on this phenomenon, with the authors demonstrating how these toxic agents take aim at the "Achilles' heel" of synapses, and better yet, how they might just be stopped.

[...] Neurobiologists at the University of California (UC) San Diego focused on a major type of synapse called glutamatergic synapses. During brain development, these synapses are pieced together by a powerful signaling pathway called the planar cell polarity (PCP) pathway, which includes signaling components called Celsr3 and Vangl2. These work in harmony to stabilize and disassemble synapses, respectively, to keep their numbers at a healthy level.

[...] The researchers then turned their attention to another key component of the PCP pathway called Ryk, which functions much like Vangl2 in mediating synapse disassembly. Using special antibodies, the scientists blocked the function of Ryk and found that this too prevented the degeneration of synapses by the amyloid beta proteins. In mouse models of Alzheimer's, both knocking out the gene for Ryk and administering the Ryk-blocking antibody protected the synapses and preserved cognitive function.

"As amyloid beta pathology and synapse loss usually occurs in early stages of Alzheimer's disease, even before cognitive decline can be detected, early intervention, such as restoring the rebalance of the PCP pathway, will likely be beneficial for Alzheimer's patients," says Zou.

The Ryk antibody also proved effective at quelling some of the signs of neuroinflammation seen in Alzheimer's, though the exact mechanisms behind this are unclear. In any case, the scientists believe these results indicate the PCP could prove a valuable target in efforts to protect synapse loss in Alzheimer's disease, and potentially other conditions.

Also at: UC San Diego

Journal Reference:
Bo Feng, Andiara E. Freitas, Lilach Gorodetski, et al. Planar cell polarity signaling components are a direct target of β-amyloid–associated degeneration of glutamatergic synapses [open], Science Advances (DOI: 10.1126/sciadv.abh2307)


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  • (Score: 1) by dcollins55 on Saturday August 21 2021, @11:56PM (8 children)

    by dcollins55 (15202) on Saturday August 21 2021, @11:56PM (#1169445)

    I will admittedly say I know little on the subject. Is it me, or does "Alzheimer's" mean a generic collection of similar symptoms, like "Cancer"? If we're only going by the common symptoms, how do we even know it's a single disease with a single cause?

    That's like saying "elevated temperature" is an illness and trying to find a way to cure it. I could have a virus, I could have a flu, I could have a foreign protein, I could be in a sauna, I could have had too much coffee, I could have just finished working out. There's no "cure for cancer because there's no single cause of Cancer - it's different mutations, in different body parts, for different reasons. I think so is Alzheimer's.

    • (Score: 2) by RS3 on Sunday August 22 2021, @12:09AM (4 children)

      by RS3 (6367) on Sunday August 22 2021, @12:09AM (#1169450)

      Completely off the cuff here, IIRC Alzheimer's is a very specific disease within a group of many brain degeneration / dementia-inducing / cognitive impairment diseases. Again, IIRC, you can only be sure it's Alzheimer's if you do tests on brain cells, which should be obvious they're not going to do on a living person.

      Quick search reveals a good read: https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/diagnosis-treatment/drc-20350453 [mayoclinic.org]

      You mentioned coffee: there seems to be controversy, as a websearch on "alzheimer's coffee" will show. It's been said and thought that coffee and caffeine are helpful in warding off Alzheimer's, but suddenly we're not so sure: https://www.marketwatch.com/story/the-latest-alzheimers-risk-coffee-11627470249 [marketwatch.com]

      • (Score: 1) by dcollins55 on Sunday August 22 2021, @12:44AM (2 children)

        by dcollins55 (15202) on Sunday August 22 2021, @12:44AM (#1169461)

        >Alzheimer's is a very specific disease

        See, to me, if we don't know the cause of something, we can't say whether it's a specific disease or several completely different ones that simply have the same outcome.

        Bronchitis is a specific illness. It can be caused by bacteria or a virus. Do you treat "Bronchitis" with an antibiotic or an antiviral? Well, maybe a bad example, a bunch of lazy doctors do instead of doing a lab or looking at the color of the loogie first.

        • (Score: 0) by Anonymous Coward on Sunday August 22 2021, @09:57PM (1 child)

          by Anonymous Coward on Sunday August 22 2021, @09:57PM (#1169689)

          if we don't know the cause of something, we can't say whether it's a specific disease

          This is a falsehood often believed by engineers, coders, and other 'first principles' workers.

          You don't need to know whether a cancer was mutated by radiation or virally or chemically induced, to know that the disease of cancer is present.

          Bronchitis is a specific illness

          It's a specific disease actually. Quoth wikipedia:

          A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not due to any immediate external injury

          Disease is the condition of the organism, not the cause.
          Disease is the condition of the organism, not the cause.

          You're thinking of root cause pathogen or dysfunction. Those are disease vectors - they make you sick! But they are not the illness or the disease. Disease is the state of the organism, NOT the cause.

          Having pedant medicos in my family, this has been a sore point. Words mean things. Disease means a thing. And not what you seem to think.

          • (Score: 0, Redundant) by dcollins55 on Sunday August 22 2021, @11:05PM

            by dcollins55 (15202) on Sunday August 22 2021, @11:05PM (#1169702)

            >You're thinking of root cause pathogen or dysfunction
            Correct. I am thinking about what the article is about, and what this whole thread is about. They took something that is defined by the symptoms and can have multiple causes, and are trying to say the symptom-based diagnosis has a single silver bullet cause. I gave many examples of why that's wrong, including bronchitis.

            Welcome to the conversation, we're glad to have you.

            >Words mean things
            Yes. You should read words before replying to words.

      • (Score: 0) by Anonymous Coward on Sunday August 22 2021, @10:57PM

        by Anonymous Coward on Sunday August 22 2021, @10:57PM (#1169699)

        You mentioned coffee...

        But of course. In our consumer-society, the solution is always consumption. If they told you the cure was severe caloric restriction and no television, nobody would do it. Give us (preferably) expensive drugs individualized to our lifestyle because we're all gluten intolerant keto paleo pescatarians.

    • (Score: 0) by Anonymous Coward on Sunday August 22 2021, @12:20AM

      by Anonymous Coward on Sunday August 22 2021, @12:20AM (#1169453)

      Alzheimer's Disease is an interesting beast. I've written before about this on this site, but the growing consensus is that AD is a family of diseases with a number of related etiological factors. Eventually, they converge into what people think of as AD proper as the disease states worsen.

    • (Score: -1, Offtopic) by Anonymous Coward on Sunday August 22 2021, @12:39AM (1 child)

      by Anonymous Coward on Sunday August 22 2021, @12:39AM (#1169460)

      Alzheimer's isn’t much of a thing unless it dominates CNN headlines - they temporarily moved on from republicans and COVID to hurricanes for the moment - cnn.com - until they find a story to terrify the next group, this may have to do - I am hoping they can get back to 80’s and 90’s style reporting if my memories are correct

      • (Score: 0) by Anonymous Coward on Sunday August 22 2021, @11:00PM

        by Anonymous Coward on Sunday August 22 2021, @11:00PM (#1169700)

        Suspect memories, I suspect...

  • (Score: 1, Interesting) by Anonymous Coward on Saturday August 21 2021, @11:59PM (3 children)

    by Anonymous Coward on Saturday August 21 2021, @11:59PM (#1169447)

    https://www.news-medical.net/news/20210628/Alzheimers-symptoms-could-be-due-to-decline-in-brain-protein-not-accumulation-of-amyloid-plaques.aspx [news-medical.net]
    "High cerebrospinal amyloid-β 42 is associated with normal cognition in individuals with brain amyloidosis": https://doi.org/10.1016/j.eclinm.2021.100988 [doi.org]

    To date, all attempts at treating Alzheimer's by attacking the plaques, consistently failed. And still, the waste of time goes on and on. Researchers cannot remember the previous results? :)

    • (Score: 4, Funny) by maxwell demon on Sunday August 22 2021, @06:30AM (2 children)

      by maxwell demon (1608) on Sunday August 22 2021, @06:30AM (#1169534) Journal

      Researchers cannot remember the previous results?

      Of course not. This is Alzheimer's research, remember?

      --
      The Tao of math: The numbers you can count are not the real numbers.
      • (Score: 0) by Anonymous Coward on Sunday August 22 2021, @06:44AM

        by Anonymous Coward on Sunday August 22 2021, @06:44AM (#1169538)

        Jesus Christ. I literally spit my drink out on that one!

      • (Score: 1, Funny) by Anonymous Coward on Sunday August 22 2021, @06:45PM

        by Anonymous Coward on Sunday August 22 2021, @06:45PM (#1169660)

        "This is Alzheimer's research, remember?"

        I forgot. Can you remind me again, what are we researching?

  • (Score: 4, Insightful) by HiThere on Sunday August 22 2021, @02:22AM (4 children)

    by HiThere (866) Subscriber Badge on Sunday August 22 2021, @02:22AM (#1169485) Journal

    The mouse model of Alzheimer's disease isn't a very good one. Many things that cure mice have no (beneficial) effect on people. It's also not at all clear that the plaques cause the problem. Several drugs that clear the plaques have been tried, and they've all failed to cure Alzheimer's. The recent one approved by the FDA is just the latest in a series, but it's the first one that got approved. However the panel of examiners strongly recommended against approving it, as there was no significant evidence of beneficial effect, and lots of evidence of serious undesired effects. They were overruled, and some resigned over that. To me it looks like either a political decision or a financial decision rather than a medical decision.

    I hope that this research has some beneficial result, and it may in decoding neural functioning. I consider it quite unlikely to have much to do with curing or preventing Alzheimer's.

    --
    Javascript is what you use to allow unknown third parties to run software you have no idea about on your computer.
    • (Score: 0) by Anonymous Coward on Sunday August 22 2021, @03:06AM (3 children)

      by Anonymous Coward on Sunday August 22 2021, @03:06AM (#1169494)

      Which mouse model do you specifically think is bad? There is more than one that work differently.

      • (Score: 2) by HiThere on Monday August 23 2021, @01:28PM (2 children)

        by HiThere (866) Subscriber Badge on Monday August 23 2021, @01:28PM (#1169847) Journal

        I haven't heard of any mouse models of Alzheimer's disease that have produced results that transferred to humans. Do you have any examples?

        --
        Javascript is what you use to allow unknown third parties to run software you have no idea about on your computer.
        • (Score: 0) by Anonymous Coward on Monday August 23 2021, @10:55PM (1 child)

          by Anonymous Coward on Monday August 23 2021, @10:55PM (#1170048)

          TAPP and PDAPP are probably the most obvious examples. Tg2576 has had some interesting results that have transferred to humans as well. Another is the paper that keeps showing up in these discussion pages as of late that "disproves" the amyloid hypothesis because it also relies on mouse model results transferring to humans.

          • (Score: 2) by HiThere on Tuesday August 24 2021, @03:18AM

            by HiThere (866) Subscriber Badge on Tuesday August 24 2021, @03:18AM (#1170138) Journal

            Searches for TAPP and PDAPP only returned results specific to mice. Tg2576 also only returned results on mice. Perhaps you could be specific on which results transmitted to humans, or point to a paper on the results.

            --
            Javascript is what you use to allow unknown third parties to run software you have no idea about on your computer.
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