7 ms·

> Instead of targeting neurons directly, this method focuses on repairing the blood-brain barrier (BBB), the brain’s defence against harmful substances. By rest

> Instead of targeting neurons directly, this method focuses on repairing the blood-brain barrier (BBB), the brain’s defence against harmful substances. By restoring proper BBB function, the researchers achieved a reversal of Alzheimer’s pathology in animal models. Alzheimer's patients often respond positively to exogenous ketone esthers, and a ketogenic diet. The proposed mechanism for this is that ketones are transported across the BBB differently than glucose. Even if glucose is unable to be transported into the brain, ketones often still are. Now that there is a drug to repair the BBB, and likely glucose transport as well, I expect the funding will mysteriously show up to properly investigate the "brain diabetes" theory of Alzheimers.

GenerWork 1y ago
>I expect the funding will mysteriously show up to properly investigate the "brain diabetes" theory of Alzheimers. There was the SNIFF [0] study that delivered insulin via nasal spray, so there's already some funding and studies happening. [0] https://www.clinicaltrials.gov/study/NCT01767909 https://www.clinicaltrials.gov/study/NCT01767909
- DANmode 1y ago
  Great share, thanks.
JumpCrisscross 1y ago
> Now that there is a drug to repair the BBB (and likely glucose transport as well), I expect the funding will mysteriously show up to properly investigate the "brain diabetes" theory of Alzheimers Why is this cast as conspiracy versus a natural consequence of risk and incentives? (‘Brain diabetes’ is in no way a neglected avenue of Alzheimer’s research.)
- matthewdgreen 1y ago
  There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientists to siphon money away from research that works. It’s a whole thing. I anssume it’s because Alzheimer’s legitimately sucks (my mom has it) and that means there has to be someone we can blame.
  - smt88 1y ago
    Wait, but isn't that "conspiracy" literally true? People faked data and everything... https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=Amyloid&sort=byPopularity&type=story https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
  - alphazard 1y ago
    > There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientist No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. That negatively affected progress in the field. You can call it "evil" if you want, but more objectively it was unaligned incentives. The corruption was covered in mainstream news, it's not a conspiracy theory. Since the scandal got out, the speed of progress has improved significantly.
    - KPGv2 1y ago
      > No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. The second sentence and the first sentence are merely literal and figurative descriptions of the same activity. Also, for this to be true, it has to mean lab workers knew about progress but fucked over their own family with Alzheimers. And it has to mean every single one of them did this. *Edit* Actually there's another way to interpret what you wrote. My mistake. I imagined a scenario where someone knew of progress and was dishonest by hiding it, but you might've been alluding to someone knowing an avenue wasn't fruitful but was dishonest by making it seem more fruitful. I think the latter is easier to hide than the former since it doesn't require directly fucking over your family, merely very indirectly by siphoning off a fraction of total funds to be flushed down the toilet.
      - feoren 1y ago
        The latter is what happened, for upwards of ten years. And it wasn't a small fraction of the funding -- almost no funding was allocated to any research not looking at amyloid plaques, because the intellectual giants' (falsified) research was showing that that was by far the most promising avenue to explore.
overgard 1y ago
I've heard the colloquial phrase "type 3 diabetes" appear a lot in talk about Alzheimers, so I'd be shocked if there isn't a lot of research going into that. I just read a book about how metabolism is related to a lot of mental disorders (depression, schizophrenia, etc.) so I think it's something that's definitely being looked at (the book is called Brain Energy, I think).
- Mabusto 1y ago
  Hey what was the book out of curiosity?
  - MrDrMcCoy 1y ago
    Probably this one: https://brainenergy.com/ https://brainenergy.com/ I've read it, it's quite good and full of citations. I've seen a number of studies since it came out that support it as well. If you like that, also check out "This is Your Brain on Food" which overlaps with much of the content there, but with a bit more of a focus on the gut brain connection.
    - SZJX 1y ago
      Change Your Diet, Change Your Mind is another book on these topics which is rather comprehensive and compelling.
ajross 1y ago
> Alzheimer's patients often respond positively to exogenous ketone esthers, and a ketogenic diet. I went looking for a cite here and came up almost empty (wikipedia has one link to an 11 year old paper that doesn't really say much authoritative in the abstract). I wish people would be more rigorous about this stuff. Atkins/paleo/keto is the gluten-free/hemp/cbd/hippy magic of the hacker set, not least because it's nearly perfect wish fulfillment[1]. And it appears in a lot of mystical contexts too, showing up as a cure for whatever is being discussed. The actual science, every time I look, is a lot less convincing. [1] Meat! It's all meat! We love meat!
- motoboi 1y ago
  Maybe you can see this as more compelling evidence: https://consensus.app/search/does-ketonic-diet-improve-alzheimer/2q7RnuSBRy2o5D_ZMCnDGg/ https://consensus.app/search/does-ketonic-diet-improve-alzhe... >Cognitive Effects and Clinical Outcomes > >Multiple systematic reviews and clinical trials report that ketogenic diets (KD) or ketone supplementation can lead to improvements in cognitive function, daily living activities, and quality of life in people with mild-to-moderate Alzheimer's disease 413141819. Chronic KD interventions (3–4 months) have been associated with increased cognitive test scores and improved memory performance 1418. Some studies also show positive changes in Alzheimer's biomarkers, such as reduced tau and increased amyloid-beta 42 in cerebrospinal fluid 7."
  - ajross 1y ago
    Well, thanks. That's certainly better than what made it into wikipedia. But honestly: no? Only 41% of papers answering "yes" to an engaging and evocative hypothesis, in the era of the replication crisis, and especially after a decade and a half of the hypothesis sitting around in general lore, generally means "no, duh" in my experience. As the site itself says, "evidence is still limited and more research is needed", which is definitely not "compelling". My money still sits on "nerd wish fulfillment". But we'll see.
    - motoboi 1y ago
      Yeah, there are studies suggesting neurons, far more so than many peripheral cells, are especially vulnerable to insulin resistance. So by the time you see systemic insulin resistance by standard measures, the brain may already be slipping. I suppose this is why ketonic diet has any role in restoring cognitive function.
epicureanideal 1y ago
Would it be possible to artificially increase the glucose in the brain to get a nootropic effect?
hinkley 1y ago
Wait… so the call doesn’t come from inside the building?? It’s crap leaking in from the rest of the body? That’s wild.
- deleted 1y ago
  [deleted]

GenerWork 1y ago

>I expect the funding will mysteriously show up to properly investigate the "brain diabetes" theory of Alzheimers. There was the SNIFF [0] study that delivered insulin via nasal spray, so there's already some funding and studies happening. [0] https://www.clinicaltrials.gov/study/NCT01767909 https://www.clinicaltrials.gov/study/NCT01767909

DANmode 1y ago
Great share, thanks.

JumpCrisscross 1y ago

> Now that there is a drug to repair the BBB (and likely glucose transport as well), I expect the funding will mysteriously show up to properly investigate the "brain diabetes" theory of Alzheimers Why is this cast as conspiracy versus a natural consequence of risk and incentives? (‘Brain diabetes’ is in no way a neglected avenue of Alzheimer’s research.)

matthewdgreen 1y ago
There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientists to siphon money away from research that works. It’s a whole thing. I anssume it’s because Alzheimer’s legitimately sucks (my mom has it) and that means there has to be someone we can blame.
- smt88 1y ago
  Wait, but isn't that "conspiracy" literally true? People faked data and everything... https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=Amyloid&sort=byPopularity&type=story https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
- alphazard 1y ago
  > There’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientist No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. That negatively affected progress in the field. You can call it "evil" if you want, but more objectively it was unaligned incentives. The corruption was covered in mainstream news, it's not a conspiracy theory. Since the scandal got out, the speed of progress has improved significantly.
  - KPGv2 1y ago
    > No one was twirling their mustache trying to make people suffer. Someone had a lab, and prestige and control over funding and the best way to keep it all was by being dishonest. The second sentence and the first sentence are merely literal and figurative descriptions of the same activity. Also, for this to be true, it has to mean lab workers knew about progress but fucked over their own family with Alzheimers. And it has to mean every single one of them did this. *Edit* Actually there's another way to interpret what you wrote. My mistake. I imagined a scenario where someone knew of progress and was dishonest by hiding it, but you might've been alluding to someone knowing an avenue wasn't fruitful but was dishonest by making it seem more fruitful. I think the latter is easier to hide than the former since it doesn't require directly fucking over your family, merely very indirectly by siphoning off a fraction of total funds to be flushed down the toilet.
    - feoren 1y ago
      The latter is what happened, for upwards of ten years. And it wasn't a small fraction of the funding -- almost no funding was allocated to any research not looking at amyloid plaques, because the intellectual giants' (falsified) research was showing that that was by far the most promising avenue to explore.

overgard 1y ago

I've heard the colloquial phrase "type 3 diabetes" appear a lot in talk about Alzheimers, so I'd be shocked if there isn't a lot of research going into that. I just read a book about how metabolism is related to a lot of mental disorders (depression, schizophrenia, etc.) so I think it's something that's definitely being looked at (the book is called Brain Energy, I think).

Mabusto 1y ago
Hey what was the book out of curiosity?
- MrDrMcCoy 1y ago
  Probably this one: https://brainenergy.com/ https://brainenergy.com/ I've read it, it's quite good and full of citations. I've seen a number of studies since it came out that support it as well. If you like that, also check out "This is Your Brain on Food" which overlaps with much of the content there, but with a bit more of a focus on the gut brain connection.
  - SZJX 1y ago
    Change Your Diet, Change Your Mind is another book on these topics which is rather comprehensive and compelling.

ajross 1y ago

> Alzheimer's patients often respond positively to exogenous ketone esthers, and a ketogenic diet. I went looking for a cite here and came up almost empty (wikipedia has one link to an 11 year old paper that doesn't really say much authoritative in the abstract). I wish people would be more rigorous about this stuff. Atkins/paleo/keto is the gluten-free/hemp/cbd/hippy magic of the hacker set, not least because it's nearly perfect wish fulfillment[1]. And it appears in a lot of mystical contexts too, showing up as a cure for whatever is being discussed. The actual science, every time I look, is a lot less convincing. [1] Meat! It's all meat! We love meat!

motoboi 1y ago
Maybe you can see this as more compelling evidence: https://consensus.app/search/does-ketonic-diet-improve-alzheimer/2q7RnuSBRy2o5D_ZMCnDGg/ https://consensus.app/search/does-ketonic-diet-improve-alzhe... >Cognitive Effects and Clinical Outcomes > >Multiple systematic reviews and clinical trials report that ketogenic diets (KD) or ketone supplementation can lead to improvements in cognitive function, daily living activities, and quality of life in people with mild-to-moderate Alzheimer's disease 413141819. Chronic KD interventions (3–4 months) have been associated with increased cognitive test scores and improved memory performance 1418. Some studies also show positive changes in Alzheimer's biomarkers, such as reduced tau and increased amyloid-beta 42 in cerebrospinal fluid 7."
- ajross 1y ago
  Well, thanks. That's certainly better than what made it into wikipedia. But honestly: no? Only 41% of papers answering "yes" to an engaging and evocative hypothesis, in the era of the replication crisis, and especially after a decade and a half of the hypothesis sitting around in general lore, generally means "no, duh" in my experience. As the site itself says, "evidence is still limited and more research is needed", which is definitely not "compelling". My money still sits on "nerd wish fulfillment". But we'll see.
  - motoboi 1y ago
    Yeah, there are studies suggesting neurons, far more so than many peripheral cells, are especially vulnerable to insulin resistance. So by the time you see systemic insulin resistance by standard measures, the brain may already be slipping. I suppose this is why ketonic diet has any role in restoring cognitive function.

epicureanideal 1y ago

Would it be possible to artificially increase the glucose in the brain to get a nootropic effect?

hinkley 1y ago

Wait… so the call doesn’t come from inside the building?? It’s crap leaking in from the rest of the body? That’s wild.

deleted 1y ago
[deleted]