8 ms·

Copper transport drug restores memory and clears toxic Alzheimer's proteins

357 points by bookofjoe 5mo ago

discretion22 5mo ago
Great news! If you are a mouse. For humans, not yet progressed to trials though safety has been evaluated for other diseases, so possible for trials to happen quickly? " the compound has strong potential to quickly transition into human clinics because it has already undergone safety evaluations for other diseases."
- functionmouse 5mo ago
  mice are having a great year
- smallerize 5mo ago
  A genetically modified mouse with human amyloid-beta peptides. https://www.jax.org/strain/004462# https://www.jax.org/strain/004462#
- onraglanroad 5mo ago
  The Hitchhiker's Guide was right. We spend all our time inventing new cures for the mice!
  - drtgh 5mo ago
    It goes even further than that. since we don’t know what causes Alzheimer’s, what they’re doing is trying to cure their own laboratory-induced symptoms in mice. It’s like trying to fix a car’s ABS system by simulating tire slippage. This is so obvious that the only thing I can think is that they simply don't care. They just want to find something that masks the symptoms (perhaps to keep patients dependent on the drug for life if they succeed). What causes Alzheimer gentlemen? very few people is really trying to solve this answer. Is it even known what causes the moments of lucidity in patients? Molecules should be mapped to identify the patterns (and therefore track possible sources).
- PrincepsZero 5mo ago
  I mean why not allow right to try for people who are already so far gone. It can potentially help them and all of us.
  - pas 5mo ago
    they can try it simply this stuff was not even at that stage. it's a lab report. there's no company making it. though there's a version of this copper complex that targets ALS, and that is already available
adamredwoods 5mo ago
Lithium, too! In mice. https://otd.harvard.edu/news/could-lithium-explain-and-treat-alzheimers-disease/ https://otd.harvard.edu/news/could-lithium-explain-and-treat...
- helterskelter 5mo ago
  Interestingly, lithium does seem to protect telomeres and in fact lengthens them, which may affect Alzheimer's.
  - alliao 5mo ago
    interesting, I remember reading population of Beijing seem to have lithium in their water or air so their new born and mothers carrying seem to have 20x of lithium concentration of what's considered normal...
    - amluto 5mo ago
      The papers suggest a plausible mechanism by which lithium orotate could have an effect that would be not present with inorganic lithium salts. IIRC the hypothesis is that lithium orotate does not fully dissociate in water and thus can cross the blood brain barrier much more easily than plain Li+, and then the cells in your brain can take up the lithium orotate, metabolize the orotate part, and make the free Li+ available.
quadhome 5mo ago
Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta. In the words of Derek Lowe: Amyloid-directed therapies truly, truly do not appear to be the answer for Alzheimer’s treatment. When I started work in the field back in the early 1990s, I was convinced of the opposite - the evidence looked very strong that defects in amyloid processing were indeed the cause of the disease. But that was thirty-five years ago, thirty-five years in which therapy after therapy after therapy aimed at amyloid mechanisms has failed. […] We’re way past persistence, way past focus, way past optimism and multiple shots on goal and old-college-tries. Do something else! For God's sake, do something else. — https://www.science.org/content/blog-post/anti-amyloid-antibodies-alzheimer-you-already-know https://www.science.org/content/blog-post/anti-amyloid-antib...
- bluGill 5mo ago
  I care what works, not about debate. This seems to work and that trumps any debate about what the real means are. Don't get me wrong, if you are in this area of research this debate is important. There may be other types of Alzheimer's that have a different means. This drug may actually target something else. There might be some other truth I haven't thought it - but to me as an outsider the important part is a treatment that works, not why it works.
  - vlovich123 5mo ago
    I don’t think anyone is against a treatment that works, regardless of the mechanism. The problem is that claimed success in these rat models has never transferred to humans. Either the problem is that rat Alzheimer’s is a poor model for human Alzheimer’s or the science being done is poor quality. > Because reducing amyloid burden is clinically proven to improve functional outcomes, these preclinical results strongly support the rationale for testing this drug in early symptomatic Alzheimer’s disease I believe this is the critical criticism of others. There’s now two camps. One side claims that the Amyloid movement is based on faulty science and outright fraud (true AFAIK) and the other side claims that there’s still evidence the amyloid hypothesis is accurate despite the flawed start to the hypothesis (possibly true). Generally I don’t trust a lot of effort being pushed behind a hypothesis that’s got such shady behavior from proponents and that rely on fast tracking drug approvals for drugs that reduce amyloids but clearly don’t benefit Alzheimer’s. Everyone gets to choose the priors they choose to evaluate the situation on.
IAmBroom 5mo ago
"Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta." That's the predominant theory, but nothing affecting them has yet proven to be efficacious so far (AFAIK). Likewise, at one time everyone "knew" aluminum was a culprit, because it showed up in autopsy analyses of affected people. However, it turned out that correlation wasn't from aluminum causing it, so avoiding aluminum didn't affect the disease.
TaupeRanger 5mo ago
Flagged. Nonsense puff piece by the university. The headline itself is beyond terrible - this is a mouse model and would need years of further successful research to be able to say that it "restores memory" in any meaningful way, let alone in actual humans.
- musiciangames 5mo ago
  Yes, it’s really disappointing to see Monash doing that - not a mention of mouse or mice.
  - contingencies 5mo ago
    AFAIK the background is the 'big 5' universities in Australia have a fat loan due which they took out 10 years ago and can't pay. Their primary income source was foreign exchange students and that demand has fallen off a cliff. So they're shedding academics and puffing like crazy right now. It seems in the near future Australian tertiary education will be highly corporatized and move to a more American model than our European-style history.
    - markdown 5mo ago
      > foreign students FTFY. Not exchange students.
      - contingencies 5mo ago
        Erp, well caught.
- Selkirk 5mo ago
  The linked article is intentionally misleading by omission because they left out "in mice" in the university driven article and they certainly know the relevance and consequences of leaving it out.
- janalsncm 5mo ago
  Press release should be replaced by actual journal article, which doesn’t omit “mouse model”.
caycep 5mo ago
..in Mice
ck2 5mo ago
btw definitely related and seems significant: they found people who use glucosamine (joint pain, knees etc) have a 25% higher chance of Alzheimer's progression https://thesciverse.org/scientists-found-that-a-supplement-taken-by-40-million-americans-for-joint-pain-is-associated-with-25-faster-progression-to-alzheimers-in-people-with-early-memory-decline/ https://thesciverse.org/scientists-found-that-a-supplement-t... (still can't figure out if that website is "AI" but they have great articles)
- plaguuuuuu 5mo ago
  Yep it's all AI-generated. It's annoying that they have a fake human as the author but whatever, it's the interslop.
- littlexsparkee 5mo ago
  note this is only the case for those with early-stage cognitive decline. for healthy individuals, it actually has neuroprotective effects. > Glucosamine mimicked the effects of a low-carbohydrate diet in a prior animal research, resulting in increased lifespan [21], and studies consistently showed that a low-carbohydrate diet protects against dementia [22, 23]. An animal study suggested that glucosamine may promote cognitive function by impacting energy metabolism [20]; other animal models have indicated the neuroprotective and anti-neuroinflammatory effects of glucosamine https://pmc.ncbi.nlm.nih.gov/articles/PMC10052856/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10052856/
avgDev 5mo ago
My mother has early onset alzheimer's disease. We currently know very little about the disease and the current treatment options are controversial. The efficacy of the medications removing the amyloid plaque from the brain is questionable, as people still decline. What makes alzheimer's difficult is that it is not really a single uniform disease. There are subtypes. Since my mother has it, I was presented with an option of a genetic test. There are several genes which increase your risk. However, if one has PSEN1 that will 100% guarantee early onset alzheimer's at some point. I'm still on the fence if I want to know. I really hope we get some viable treatments for this terrible disease. Early onset azlheimer's is awful. I cannot imagine having malfunctioning brain.
- nphardon 5mo ago
  How old is your mother? Iirc PSEN1 correlates to very early AD, like late 30s early 40s. My dad had full blown AD at 65, with serious cognitive decline starting at 63, and that felt very early to us all. My dad had no AD biomarkers on full genetic scan. My heart goes out to you and your family.
  - avgDev 5mo ago
    She is now 63. Started showing symptoms at 61. Her sister died at 64 and her onset was in her 50s. I am working with invitae to get her DNA tested. Unfortunately, her stage is considered moderate and very little treatment options.
  - armadsen 5mo ago
    There are multiple specific possible mutations that cause 100% penetrant dominantly inherited early onset Alzheimer’s. And there are three genes where mutations can cause it: PSEN1, PSEN2, and APP. The average age of onset seems to depend on the specific mutation. In my (wife’s) family, onset is mid 40s to mid 50s. Some families get it even earlier, but 30s seems rare.
- marton78 5mo ago
  Give her -- and yourself -- lithium orotate. It's an asymmetric bet: it won't hurt, but very well might help. It has been found to be effective in murine models.
djray 5mo ago
This pertinent paper appeared more than a decade ago about the flaws in the amyloid plaque hypothesis: https://pmc.ncbi.nlm.nih.gov/articles/PMC4207354/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4207354/ Many people without dementia show amyloid plaques in their brains in autopsies. It's becoming more accepted now that there are multiple interrelated causes after decades pursuing the simplistic amyloid plaque theory. The article is bordering on irresponsible.
ebolyen 5mo ago
I think people are reacting to the press-release more than the work. I don't see why this is definitely doomed just because they discuss beta-amyloid plaques. Those exist and are real. They probably don't cause it any more than tombstones cause graveyards; very related, but not in the directly mechanistic way we wish. > Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) peptides in the brain. This can be true and still not be the specific mechanism. You can treat a specific waste product or you can repair the waste stream. The issue may be waste, but not a specific product, or the issue may not be the waste stream at all. This work appears to demonstrate evidence of waste stream repair via a well-known waste-product. That doesn't mean that any specific waste product is or is not the problem or that this particular stream is definitely going to remove enough of the waste (if that was the problem). Maybe there have been a lot of drugs which have similarly attempted waste-stream repair so there's good reason to doubt it on that alone. But I don't think that mentioning beta-amyloid plaque is enough to discard this out-of-hand.
- yxhuvud 5mo ago
  It is also worth mentioning that many of the alternative explanations involve brain infection, and improving brain/blood barrier also apply to that.
mlmonkey 5mo ago
In some parts of the world, it is recommended that drinking water be stored in copper containers. I'm wondering if these communities had figured something out about the health benefits of ingesting trace amounts of copper?
- pengaru 5mo ago
  There's no need for missing answers as to why copper is appreciated as a water transport/storage medium. It's the same reason it's traditionally used as cladding on boat hulls, and is still added to many anti-fouling bottom paints - it's antimicrobial, but also toxic.
mannyv 5mo ago
Anything that might fix brain plumbing would be welcome. Over time, everything breaks down. If this actually fixes some plumbing issue that would be great. Of course, it probably will lead to another downstream plumbing issue, but one thing at a time.
janalsncm 5mo ago
Maybe a slight problem is liver toxicity at the doses in this study? The drug was tested at lower doses for other diseases, but above 72 mg caused problems. Quick conversion math is telling me this study would want 170+ mg. Maybe there’s some way to get around this particular issue.
adaml_623 5mo ago
I think it's immoral and unkind to report on a medical trial and not be clear that it was in mice rather than humans.
phyzome 5mo ago
IN MICE
layla5alive 5mo ago
A lot of people here in the comments saying 'this can't work because amyloid beta hypothesis was wrong' seem to be missing that this treatment is aimed at some of the primary mediators of general brain health (function of natural BBB/vascular waste clearance mechanisms, which seem to degenerate over time, and modulation of neuroinflammation), not just clearing AB proteins pharmacologically. This jibes well with the stated improvements in Parkinsons and ALS. I doubt there is one root cause of Alzheimers (except maybe in some genetic cases), and this is likely not a panacea, but sounds like it may assist some of the key processes involved in breakdown. Root behaviors related to sleep quality and quantity, diet, exercise, infection, environmental exposure and stress, as well as genetics, likely all contribute. But, waste clearing and neuro-inflammation seem to be core processes involved in the progression of the pathology, and improving natural vascular waste clearance seems like a logical place to find at least a small improvement in progression and symptoms... Analogy: if someone puts metal shavings in an engine, having a better oil filter won't prevent all damage caused by the person putting the metal shavings there (nor will it halt the process), but it will reduce the damage by getting those shavings out of circulation before they have a chance to make even more repeated passes through the engine and do even more more damage. Improved vascular waste clearance is likely only a small piece of the puzzle, like having good oil pressure and filtration, but that doesn't mean it's irrelevant just because it doesn't prevent the other upstream root causes!

357 points by bookofjoe 5mo ago

Great news! If you are a mouse. For humans, not yet progressed to trials though safety has been evaluated for other diseases, so possible for trials to happen quickly? " the compound has strong potential to quickly transition into human clinics because it has already undergone safety evaluations for other diseases."

functionmouse 5mo ago
mice are having a great year
smallerize 5mo ago
A genetically modified mouse with human amyloid-beta peptides. https://www.jax.org/strain/004462# https://www.jax.org/strain/004462#
onraglanroad 5mo ago
The Hitchhiker's Guide was right. We spend all our time inventing new cures for the mice!
- drtgh 5mo ago
  It goes even further than that. since we don’t know what causes Alzheimer’s, what they’re doing is trying to cure their own laboratory-induced symptoms in mice. It’s like trying to fix a car’s ABS system by simulating tire slippage. This is so obvious that the only thing I can think is that they simply don't care. They just want to find something that masks the symptoms (perhaps to keep patients dependent on the drug for life if they succeed). What causes Alzheimer gentlemen? very few people is really trying to solve this answer. Is it even known what causes the moments of lucidity in patients? Molecules should be mapped to identify the patterns (and therefore track possible sources).
PrincepsZero 5mo ago
I mean why not allow right to try for people who are already so far gone. It can potentially help them and all of us.
- pas 5mo ago
  they can try it simply this stuff was not even at that stage. it's a lab report. there's no company making it. though there's a version of this copper complex that targets ALS, and that is already available

adamredwoods 5mo ago

Lithium, too! In mice. https://otd.harvard.edu/news/could-lithium-explain-and-treat-alzheimers-disease/ https://otd.harvard.edu/news/could-lithium-explain-and-treat...

helterskelter 5mo ago
Interestingly, lithium does seem to protect telomeres and in fact lengthens them, which may affect Alzheimer's.
- alliao 5mo ago
  interesting, I remember reading population of Beijing seem to have lithium in their water or air so their new born and mothers carrying seem to have 20x of lithium concentration of what's considered normal...
  - amluto 5mo ago
    The papers suggest a plausible mechanism by which lithium orotate could have an effect that would be not present with inorganic lithium salts. IIRC the hypothesis is that lithium orotate does not fully dissociate in water and thus can cross the blood brain barrier much more easily than plain Li+, and then the cells in your brain can take up the lithium orotate, metabolize the orotate part, and make the free Li+ available.

quadhome 5mo ago

Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta. In the words of Derek Lowe: Amyloid-directed therapies truly, truly do not appear to be the answer for Alzheimer’s treatment. When I started work in the field back in the early 1990s, I was convinced of the opposite - the evidence looked very strong that defects in amyloid processing were indeed the cause of the disease. But that was thirty-five years ago, thirty-five years in which therapy after therapy after therapy aimed at amyloid mechanisms has failed. […] We’re way past persistence, way past focus, way past optimism and multiple shots on goal and old-college-tries. Do something else! For God's sake, do something else. — https://www.science.org/content/blog-post/anti-amyloid-antibodies-alzheimer-you-already-know https://www.science.org/content/blog-post/anti-amyloid-antib...

bluGill 5mo ago
I care what works, not about debate. This seems to work and that trumps any debate about what the real means are. Don't get me wrong, if you are in this area of research this debate is important. There may be other types of Alzheimer's that have a different means. This drug may actually target something else. There might be some other truth I haven't thought it - but to me as an outsider the important part is a treatment that works, not why it works.
- vlovich123 5mo ago
  I don’t think anyone is against a treatment that works, regardless of the mechanism. The problem is that claimed success in these rat models has never transferred to humans. Either the problem is that rat Alzheimer’s is a poor model for human Alzheimer’s or the science being done is poor quality. > Because reducing amyloid burden is clinically proven to improve functional outcomes, these preclinical results strongly support the rationale for testing this drug in early symptomatic Alzheimer’s disease I believe this is the critical criticism of others. There’s now two camps. One side claims that the Amyloid movement is based on faulty science and outright fraud (true AFAIK) and the other side claims that there’s still evidence the amyloid hypothesis is accurate despite the flawed start to the hypothesis (possibly true). Generally I don’t trust a lot of effort being pushed behind a hypothesis that’s got such shady behavior from proponents and that rely on fast tracking drug approvals for drugs that reduce amyloids but clearly don’t benefit Alzheimer’s. Everyone gets to choose the priors they choose to evaluate the situation on.

IAmBroom 5mo ago

"Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta." That's the predominant theory, but nothing affecting them has yet proven to be efficacious so far (AFAIK). Likewise, at one time everyone "knew" aluminum was a culprit, because it showed up in autopsy analyses of affected people. However, it turned out that correlation wasn't from aluminum causing it, so avoiding aluminum didn't affect the disease.

TaupeRanger 5mo ago

Flagged. Nonsense puff piece by the university. The headline itself is beyond terrible - this is a mouse model and would need years of further successful research to be able to say that it "restores memory" in any meaningful way, let alone in actual humans.

musiciangames 5mo ago
Yes, it’s really disappointing to see Monash doing that - not a mention of mouse or mice.
- contingencies 5mo ago
  AFAIK the background is the 'big 5' universities in Australia have a fat loan due which they took out 10 years ago and can't pay. Their primary income source was foreign exchange students and that demand has fallen off a cliff. So they're shedding academics and puffing like crazy right now. It seems in the near future Australian tertiary education will be highly corporatized and move to a more American model than our European-style history.
  - markdown 5mo ago
    > foreign students FTFY. Not exchange students.
    - contingencies 5mo ago
      Erp, well caught.
Selkirk 5mo ago
The linked article is intentionally misleading by omission because they left out "in mice" in the university driven article and they certainly know the relevance and consequences of leaving it out.
janalsncm 5mo ago
Press release should be replaced by actual journal article, which doesn’t omit “mouse model”.

caycep 5mo ago

..in Mice

ck2 5mo ago

btw definitely related and seems significant: they found people who use glucosamine (joint pain, knees etc) have a 25% higher chance of Alzheimer's progression https://thesciverse.org/scientists-found-that-a-supplement-taken-by-40-million-americans-for-joint-pain-is-associated-with-25-faster-progression-to-alzheimers-in-people-with-early-memory-decline/ https://thesciverse.org/scientists-found-that-a-supplement-t... (still can't figure out if that website is "AI" but they have great articles)

plaguuuuuu 5mo ago
Yep it's all AI-generated. It's annoying that they have a fake human as the author but whatever, it's the interslop.
littlexsparkee 5mo ago
note this is only the case for those with early-stage cognitive decline. for healthy individuals, it actually has neuroprotective effects. > Glucosamine mimicked the effects of a low-carbohydrate diet in a prior animal research, resulting in increased lifespan [21], and studies consistently showed that a low-carbohydrate diet protects against dementia [22, 23]. An animal study suggested that glucosamine may promote cognitive function by impacting energy metabolism [20]; other animal models have indicated the neuroprotective and anti-neuroinflammatory effects of glucosamine https://pmc.ncbi.nlm.nih.gov/articles/PMC10052856/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10052856/

avgDev 5mo ago

My mother has early onset alzheimer's disease. We currently know very little about the disease and the current treatment options are controversial. The efficacy of the medications removing the amyloid plaque from the brain is questionable, as people still decline. What makes alzheimer's difficult is that it is not really a single uniform disease. There are subtypes. Since my mother has it, I was presented with an option of a genetic test. There are several genes which increase your risk. However, if one has PSEN1 that will 100% guarantee early onset alzheimer's at some point. I'm still on the fence if I want to know. I really hope we get some viable treatments for this terrible disease. Early onset azlheimer's is awful. I cannot imagine having malfunctioning brain.

nphardon 5mo ago
How old is your mother? Iirc PSEN1 correlates to very early AD, like late 30s early 40s. My dad had full blown AD at 65, with serious cognitive decline starting at 63, and that felt very early to us all. My dad had no AD biomarkers on full genetic scan. My heart goes out to you and your family.
- avgDev 5mo ago
  She is now 63. Started showing symptoms at 61. Her sister died at 64 and her onset was in her 50s. I am working with invitae to get her DNA tested. Unfortunately, her stage is considered moderate and very little treatment options.
- armadsen 5mo ago
  There are multiple specific possible mutations that cause 100% penetrant dominantly inherited early onset Alzheimer’s. And there are three genes where mutations can cause it: PSEN1, PSEN2, and APP. The average age of onset seems to depend on the specific mutation. In my (wife’s) family, onset is mid 40s to mid 50s. Some families get it even earlier, but 30s seems rare.
marton78 5mo ago
Give her -- and yourself -- lithium orotate. It's an asymmetric bet: it won't hurt, but very well might help. It has been found to be effective in murine models.

djray 5mo ago

This pertinent paper appeared more than a decade ago about the flaws in the amyloid plaque hypothesis: https://pmc.ncbi.nlm.nih.gov/articles/PMC4207354/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4207354/ Many people without dementia show amyloid plaques in their brains in autopsies. It's becoming more accepted now that there are multiple interrelated causes after decades pursuing the simplistic amyloid plaque theory. The article is bordering on irresponsible.

ebolyen 5mo ago

I think people are reacting to the press-release more than the work. I don't see why this is definitely doomed just because they discuss beta-amyloid plaques. Those exist and are real. They probably don't cause it any more than tombstones cause graveyards; very related, but not in the directly mechanistic way we wish. > Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) peptides in the brain. This can be true and still not be the specific mechanism. You can treat a specific waste product or you can repair the waste stream. The issue may be waste, but not a specific product, or the issue may not be the waste stream at all. This work appears to demonstrate evidence of waste stream repair via a well-known waste-product. That doesn't mean that any specific waste product is or is not the problem or that this particular stream is definitely going to remove enough of the waste (if that was the problem). Maybe there have been a lot of drugs which have similarly attempted waste-stream repair so there's good reason to doubt it on that alone. But I don't think that mentioning beta-amyloid plaque is enough to discard this out-of-hand.

yxhuvud 5mo ago
It is also worth mentioning that many of the alternative explanations involve brain infection, and improving brain/blood barrier also apply to that.

mlmonkey 5mo ago

In some parts of the world, it is recommended that drinking water be stored in copper containers. I'm wondering if these communities had figured something out about the health benefits of ingesting trace amounts of copper?

pengaru 5mo ago
There's no need for missing answers as to why copper is appreciated as a water transport/storage medium. It's the same reason it's traditionally used as cladding on boat hulls, and is still added to many anti-fouling bottom paints - it's antimicrobial, but also toxic.

mannyv 5mo ago

Anything that might fix brain plumbing would be welcome. Over time, everything breaks down. If this actually fixes some plumbing issue that would be great. Of course, it probably will lead to another downstream plumbing issue, but one thing at a time.

janalsncm 5mo ago

Maybe a slight problem is liver toxicity at the doses in this study? The drug was tested at lower doses for other diseases, but above 72 mg caused problems. Quick conversion math is telling me this study would want 170+ mg. Maybe there’s some way to get around this particular issue.

adaml_623 5mo ago

I think it's immoral and unkind to report on a medical trial and not be clear that it was in mice rather than humans.

phyzome 5mo ago

IN MICE

layla5alive 5mo ago

A lot of people here in the comments saying 'this can't work because amyloid beta hypothesis was wrong' seem to be missing that this treatment is aimed at some of the primary mediators of general brain health (function of natural BBB/vascular waste clearance mechanisms, which seem to degenerate over time, and modulation of neuroinflammation), not just clearing AB proteins pharmacologically. This jibes well with the stated improvements in Parkinsons and ALS. I doubt there is one root cause of Alzheimers (except maybe in some genetic cases), and this is likely not a panacea, but sounds like it may assist some of the key processes involved in breakdown. Root behaviors related to sleep quality and quantity, diet, exercise, infection, environmental exposure and stress, as well as genetics, likely all contribute. But, waste clearing and neuro-inflammation seem to be core processes involved in the progression of the pathology, and improving natural vascular waste clearance seems like a logical place to find at least a small improvement in progression and symptoms... Analogy: if someone puts metal shavings in an engine, having a better oil filter won't prevent all damage caused by the person putting the metal shavings there (nor will it halt the process), but it will reduce the damage by getting those shavings out of circulation before they have a chance to make even more repeated passes through the engine and do even more more damage. Improved vascular waste clearance is likely only a small piece of the puzzle, like having good oil pressure and filtration, but that doesn't mean it's irrelevant just because it doesn't prevent the other upstream root causes!