An Accessible New Development Against Alzheimer’s

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Dopamine vs Alzheimer’s

One of the key hallmarks of Alzheimer’s disease is the formation of hardened beta-amyloid plaques around neurons. The beta-amyloid peptides themselves are supposed to be in the brain, but the hardened pieces of them that form the plaques are not.

While the full nature of the relationship between those plaques and Alzheimer’s disease is not known for sure (there are likely other factors involved, and “the amyloid hypothesis” is at this stage nominally just that, a hypothesis), one thing that has been observed is that increasing or reducing the plaques increases or reduces (respectively) Alzheimer’s symptoms such as memory loss.

Neprilysin

There is an enzyme, neprilysin, that can break down those plaques.

Neprilysin is made naturally in the brain, and/but we cannot take it as a supplement or medication, because it’s too big to pass through the blood-brain barrier.

A team of researchers led by Dr. Takaomi Saido genetically manipulated mice to produce more neprilysin, and those mice resultantly experienced fewer beta-amyloid plaques and better memory in their old age.

However wonderful for the mice (and a great proof of principle) the above approach is not useful as a treatment for humans whose genomes weren’t modified at our conception in a lab.

Since (as mentioned before) we also can’t take it as a medication/supplement, that leaves one remaining option: find a way to make our already-existing brains produce more of it.

The team’s previous research allowed them to narrow this down to “there is probably a hormone made in the hypothalamus that modulates this”, so they began experimenting with making the mice produce more hormones there.

The DREADD switch

DREADDs, or Designer Receptors Exclusively Activated by Designer Drugs, were the next tool in the toolbox. The scientists attached these designer receptors to dopamine-producing neurons in the mice, so that they could be activated by the appropriate designer drugs—basically, allowing for a “make more dopamine” button, without having to literally wire up the brains with electrodes. The “button” gets triggered instead by a chemical trigger, the designer drug. You can read more about them here:

DREADDs for Neuroscientists: A Primer

The result was positive; when the mice made more dopamine, the result was that they also made more neprilysin. So far, the hypothesis is that the presence of dopamine upregulates the production of neprilysin. In other words, the increased neprilysin levels were caused by the increased dopamine levels (the alternatives would have been: they were both caused by the same thing—in this case that’d be the DREADD activation—or the increase was caused by something else entirely that hadn’t been controlled for).

As to how the causal relationship was determined…

“But I don’t have (or want) a DREADD switch in my head”

Happily for us (and probably happily for the mice too, because dopamine causes feelings of happiness), the experiments continued.

This time, instead of using the DREADD system, they tried simply supplementing the mouse food with l-dopa, a dopamine precursor. L-dopa is often used in the treatment of Parkinson’s disease, because the molecules are small enough to pass through the blood-brain barrier, and can be converted to full dopamine inside the brain itself. So, taking l-dopa normally raises dopamine levels.

The results? The mice who were given l-dopa enjoyed:

  • higher dopamine levels
  • higher neprilysin levels
  • lower beta-amyloid plaque levels
  • better memory in tests

The next step for the researchers is to investigate how exactly dopamine regulates neprilysin in the brain, but for now, the relationship between l-dopa consumption and the reduction of Alzheimer’s symptoms seems clear.

You can read about the study here:

The dopaminergic system promotes neprilysin-mediated degradation of amyloid-β in the brain

Is there a catch?

L-dopa has common side effects that are not pleasant; the list begins with nausea and vomiting, and continues with things that one might expect from having “too much of a good thing” when it comes to dopamine, such as dyskinesia (extra movements) and hallucinations.

You can read about it more here at the Parkinson’s Foundation:

Parkinson’s Foundation | Levodopa

However! All is not lost. Rather than reaching for the heavy guns by taking l-dopa unnecessarily, there are other dopamine precursors that don’t have those side effects (and are consequently less restricted, to the point they can be purchased as supplements, or indeed, enjoyed where they occur naturally in some foods).

Top of the list of such safe* and readily-available dopamine precursors is…

N-Acetyl L-Tyrosine (NALT): The Dopamine Precursor & More

If you’d like to try that, here’s an example product on Amazon… Or you could eat fish, white beans, tofu, natto, or pumpkin seeds 😉

*Quick note on safety: “safe” is a relative term and may vary from person to person. Please speak with your own doctor to be sure, check with your pharmacist in case of any meds interactions, and be especially careful taking anything that increases dopamine levels if you have bipolar disorder or are otherwise prone to psychosis of any kind. For most people, this shouldn’t be an issue as our brains have a built-in mechanism for scrubbing excess dopamine and ensuring we don’t end up with too much, but for some people whose dopamine regulation is not so good in that regard, it can cause problems. So again, speak with your doctor to be sure, because we are not doctors, let alone your doctor.

Lastly…

If you’d like an entirely drug-free approach, that’s skipping even the “nutraceuticals”, you might enjoy:

Short On Dopamine? Science Has The Answer

Take care!

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  • Hold Me Tight – by Dr. Sue Johnson

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    A lot of relationship books are quite wishy-washy. This one isn’t.

    This one is evidenced-based (and heavily referenced!), and yet at the same time as being deeply rooted in science, it doesn’t lose the human touch.

    Dr. Johnson has spent her career as a clinical psychologist and researcher; she’s the primary developer of Emotionally Focused Therapy (EFT), which has demonstrated its effectiveness in over 35 years of peer-reviewed clinical research. In other words, it works.

    EFT—and thus also this book—finds roots in Attachment Theory. As such, topics this book covers include:

    • Recognizing and recovering from attachment injury
    • How fights in a relationship come up, and how they can be avoided
    • How lot of times relationships end, it’s not because of fights, but a loss of emotional connection
    • Building a lifetime of love instead, falling in love again each day

    This book lays the groundwork for ensuring a strong, secure, ongoing emotional bond, of the kind that makes/keeps a relationship joyful and fulfilling.

    Dr. Johnson has been recognized in her field with a Lifetime Achievement Award, and the Order of Canada.

    Get your copy of Hold Me Tight from Amazon today!

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  • Beyond Balancing The Books – by George Marino, CPA, CFP

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    We hear a lot about the importance of mindfulness, yet how can Zen-like non-attachment to the material world go well with actually surviving (let alone thriving) in a Capitalist society?

    Books that try to connect the two often end up botching it badly to the level of early 2000s motivational posters.

    So, what does this book do differently? Mostly it’s because rather than a motivational speech with exhortations to operate on a higher plain and manifest your destiny and all that, it gives practical, down-to-earth advice and offers small simple things you can do or change to mindfully engage with the world of business rather than operating on auto-pilot.

    Basically: how to cut out the stress without cutting out your performance.

    All in all, we think both your health and your productivity will thank you for it!

    Take Your Business (and Brain) “Beyond Balancing The Books” Today

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  • An Elegant Defense – by Matt Richtel

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    In a way, Richtel got the best and worst of the publication date lottery. This book, which he’d obviously been working on for however long, was published in March 2020. Yes, that March 2020. So, it obviously got a huge boost in sales that launced it to bestseller status, and/but it doesn’t actually discuss COVID at all.

    What it does discuss, is—as one might expect—the immune system. Or really, the immune systems, plural, several systems working alongside each other. How we got to have such, how our immune functions work, where all the various immune cells come from and what part they play. What pathogens can do to fight and/or confuse (or even co-opt) our immune response, and what modern medicine can do to counteract the pathogens’ anti-countermeasure countermeasures. And how it can still go wrong.

    The “Four Lives” promised in the subtitle are stories, and Richtel explains the immune system through specific people’s specific battles. In particular, a friend of his who had quite a remarkable battle against cancer, which was of course terrible for him, but illustrative for us.

    The style of the book is very readably journalistic. The author is a Pulitzer-winning NYT journalist, and not normally a science writer. Here at 10almonds, “we like big bibliographies and we cannot lie”, and we didn’t get to enjoy that in this case. The book contained no bibliography (nor appropriate inline citations, nor equivalent footnotes). Maybe a future addition will include this.

    Bottom line: there’s a lot of “science for the lay reader” here. While the lack of references is a big oversight, the book does give a very good overview of what both sides (immune response and pathogenic invasion) bring to the battle of your body.

    Click here to check out Elegant Defense, and demystify immunology!

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Related Posts

  • Our ‘food environments’ affect what we eat. Here’s how you can change yours to support healthier eating
  • How To Boost Your Memory Immediately (Without Supplements)

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    How To Boost Your Memory (Without Supplements)

    While we do recommend having a good diet and taking advantage of various supplements that have been found to help memory, that only gets so much mileage. With that in mind…

    First, how good is your memory? Take This 2-Minute Online Test

    Now, that was a test of short term memory, which tends to be the most impactful in our everyday life.

    It’s the difference between “I remember the address of the house where I grew up” (long-term memory) and “what did I come to this room to do?” (short-term memory / working memory)

    First tip:

    When you want to remember something, take a moment to notice the details. You can’t have a madeleine moment years later if you wolfed down the madeleines so urgently they barely touched the sides.

    This goes for more than just food, of course. And when facing the prospect of age-related memory loss in particular, people tend to be afraid not of forgetting their PIN code, but their cherished memories of loved ones. So… Cherish them, now! You’ll struggle to cherish them later if you don’t cherish them now. Notice the little details as though you were a painter looking at a scene for painting. Involve more senses than just sight, too!

    If it’s important, relive it. Relive it now, relive it tomorrow. Rehearsal is important to memory, and each time you relive a memory, the deeper it gets written into your long-term memory until it becomes indelible to all but literal brain damage.

    Second tip:

    Tell the story of it to someone else. Or imagine telling it to someone else! (You brain can’t tell the difference)

    And you know how it goes… Once you’ve told a story a few times, you’ll never forget it later. Isn’t your life a story worth telling?

    Many people approach memory like they’re studying for a test. Don’t. Approach it like you’re preparing to tell a story, or give a performance. We are storytelling creatures at heart, whether or not we realize it.

    What do you do when you find yourself in a room and wonder why you went there? (We’ve all been there!) You might look around for clues, but if that doesn’t immediately serve, your fallback will be retracing your steps. Literally, physically, if needs be, but at least mentally. The story of how you got there is easier to remember than the smallest bit of pure information.

    What about when there’s no real story to tell, but we still need to remember something?

    Make up a story. Did you ever play the game “My granny went to market” as a child?

    If not, it’s a collaborative memory game in which players take turns adding items to a list, “My granny went to market and bought eggs”, My granny went to market and bought eggs and milk”, “my granny went to market and bought eggs and milk and flour” (is she making a cake?), “my granny went to market and bought eggs and milk and flour and shoe polish” (what image came to mind? Use that) “my granny went to market and bought eggs and milk and flour and shoe polish and tea” (continue building the story in your head), and so on.

    When we actually go shopping, if we don’t have a written list we may rely on the simple story of “what I’m going to cook for dinner” and walking ourselves through that story to ensure we get the things we need.

    This is because our memory thrives (and depends!) on connections. Literal synapse connections in the brain, and conceptual contextual connections in your mind. The more connections, the better the memory.

    Now imagine a story: “I went to Stonehenge, but in the background was a twin-peaked mountain blue. I packed a red suitcase, placing a conch shell inside it, when suddenly I heard a trombone, and…” Ring any bells? These are example items from the memory test earlier, though of course you may have seen different things in a different order.

    So next time you want to remember things, don’t study as though for a test. Prepare to tell a story!

    Try going through the test again, but this time, ignore their instructions because we’re going to use the test differently than intended (we’re rebels like that). Don’t rush, and don’t worry about the score this time (or even whether or not you saw a given image previously), but instead, build a story as you go. We’re willing to bet that after it, you can probably recite most of the images you saw in their correct order with fair confidence.

    Here’s the link again: Take The Same Test, But This Time Make It Story-Worthy!

    Again, ignore what it says about your score this time, because we weren’t doing that this time around. Instead, list the things you saw.

    What you were just able to list was the result of you doing story-telling with random zero-context images while under time pressure.

    Imagine what you can do with actual meaningful memories of your ongoing life, people you meet, conversations you have!

    Just… Take the time to smell the roses, then rehearse the story you’ll tell about them. That memory will swiftly become as strong as any memory can be, and quickly get worked into your long-term memory for the rest of your days.

    Don’t Forget…

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    Learn to Age Gracefully

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  • South Indian-Style Chickpea & Mango Salad

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    We have a double-dose of chickpeas today, but with all the other ingredients, this dish is anything but boring. Fun fact about chickpeas though: they’re rich in sitosterol, a plant sterol that, true to its name, sits on cholesterol absorption sites, reducing the amount of dietary cholesterol absorbed. If you are vegan, this will make no difference to you because your diet does not contain cholesterol, but for everyone else, this is a nice extra bonus!

    You will need

    • 1 can white chickpeas, drained and rinsed
    • 1 can black chickpeas (kala chana), drained and rinsed
    • 9 oz fresh mango, diced (or canned is fine if that’s what’s available)
    • 1½ oz ginger, peeled and grated
    • 2 green chilis, finely chopped (adjust per heat preferences)
    • 2 tbsp desiccated coconut (or 3 oz grated coconut, if you have it fresh)
    • 8 curry leaves (dried is fine if that’s what’s available)
    • 1 tsp mustard seeds
    • 1 tsp cumin seeds
    • 1 tsp black pepper, coarse ground
    • ½ tsp MSG or 1 tsp low-sodium salt
    • Juice of 1 lime
    • Extra virgin olive oil

    Method

    (we suggest you read everything at least once before doing anything)

    1) Heat some oil in a skillet over a medium heat. When it’s hot but not smoking, add the ginger, chilis, curry leaves, mustard seeds, and cumin seeds, stirring well to combine, keep going until the mustard seeds start popping.

    2) Add the chickpeas (both kinds), as well as the black pepper and the MSG/salt. Once they’re warm through, take it off the heat.

    3) Add the mango, coconut, and lime juice, mixing thoroughly.

    4) Serve warm, at room temperature, or cold:

    Enjoy!

    Want to learn more?

    For those interested in some of the science of what we have going on today:

    Take care!

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  • Stop Pain Spreading

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Put Your Back Into It (Or Don’t)!

    We’ve written before about Managing Chronic Pain (Realistically!), and today we’re going to tackle a particular aspect of chronic pain management.

    • It’s a thing where the advice is going to be “don’t do this”
    • And if you have chronic pain, you will probably respond “yep, I do that”

    However, it’s definitely a case of “when knowing isn’t the problem”, or at the very least, it’s not the whole problem.

    Stop overcompensating and address the thing directly

    We all do it, whether in chronic pain, or just a transient injury. But we all need to do less of it, because it causes a lot of harm.

    Example: you have pain in your right knee, so you sit, stand, walk slightly differently to try to ease that pain. It works, albeit marginally, at least for a while, but now you also have pain in your left hip and your lumbar vertebrae, because of how you leaned a certain way. You adjust how you sit, stand, walk, to try to ease both sets of pain, and before you know it, now your neck also hurts, you have a headache, and you’re sure your digestion isn’t doing what it should and you feel dizzy when you stand. The process continues, and before long, what started off as a pain in one knee has now turned your whole body into a twisted aching wreck.

    What has happened: the overcompensation due to the original pain has unduly stressed a connected part of the body, which we then overcompensate for somewhere else, bringing down the whole body like a set of dominoes.

    For more on this: Understanding How Pain Can Spread

    “Ok, but how? I can’t walk normally on that knee!”

    We’re keeping the knee as an example here, but please bear in mind it could be any chronic pain and resultant disability.

    Note: if you found the word “disability” offputting, please remember: if it adversely affects your abilities, it is a disability. Disabilities are not something that only happen to other people! They will happen to most of us at some point!

    Ask yourself: what can you do, and what can’t you do?

    For example:

    • maybe you can walk, but not normally
    • maybe you can walk normally, but not without great pain
    • maybe you can walk normally, but not at your usual walking pace

    First challenge: accept your limitations. If you can’t walk at your usual walking pace without great pain and/or throwing your posture to the dogs, then walk more slowly. To Hell with societal expectations that it shouldn’t take so long to walk from A to B. Take the time you need.

    Second challenge: accept help. It doesn’t have to be help from another person (although it could be). It might be accepting the help of a cane, or maybe even a wheelchair for “flare-up” days. Society, especially American society which is built on ideas of self-sufficiency, has framed a lot of such options as “giving up”, but if they help you get about your day while minimizing doing further harm to your body, then they can be good and even health-preserving things. Same goes for painkillers if they help you from doing more harm to your body by balling up tension in a part of your body in a way that ends up spreading out and laying ruin to your whole body.

    Speaking of which:

    How Much Does It Hurt? Get The Right Help For Your Pain

    After which, you might want to check out:

    The 7 Approaches To Pain Management

    and

    Science-Based Alternative Pain Relief

    Third challenge: deserves its own section, so…

    Do what you can

    If you have chronic pain (or any chronic illness, really), you are probably fed up of hearing how this latest diet will fix you, or yoga will fix you, and so on. But, while these things may not be miracle cures…

    • A generally better diet really will lessen symptoms and avoid flare-ups (a low-inflammation diet is a great start for lessening the symptoms of a lot of chronic illnesses)
    • Doing what exercise you can, being mindful of your limitations yes but still keeping moving as much as possible, will also prevent (or at least slow) deterioration. Consider consulting a physiotherapist for guidance (a doctor will more likely just say “rest, take it easy”, whereas a physiotherapist will be able to give more practical advice).
    • Getting good sleep may be a nightmare in the case of chronic pain (or other chronic illnesses! Here’s to those late night hyperglycemia incidents for Type 1 Diabetics that then need monitoring for the next few hours while taking insulin and hoping it goes back down) but whatever you can do to prioritize it, do it.

    Want to read more?

    We reviewed a little while ago a great book about this; the title sounds like a lot of woo, but we promise the content is extremely well-referenced science:

    The Pain Relief Secret: How to Retrain Your Nervous System, Heal Your Body, and Overcome Chronic Pain – by Sarah Warren

    …and if your issue is back pain specifically, we highly recommend:

    Healing Back Pain: The Mind-Body Connection – by Dr. John Sarno

    Take care!

    Don’t Forget…

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    Learn to Age Gracefully

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