4 ms·

Nasal spray could prevent Alzheimer’s disease, brain inflammation

114 points by happyopossum 5y ago

donkeydoug 5y ago
.... in mice.
- rzzzt 5y ago
  Indeed, from the LSU Health announcement: "The study uses the AppNL-G-F/NL-G-F mouse model for AD."
Damogran6 5y ago
Wife has a genetic predisposition towards Alzheimer's...All of these articles both fill me with hope and dread at the same time. We watched her Father and Grandfather succumb and I'm so hopeful something will be found and come to bear in time to help her if she needs it.
- jjtheblunt 5y ago
  how do they know it's genetic and not environmental?
  - busyant 5y ago
    https://en.wikipedia.org/wiki/Apolipoprotein_E#Alzheimer's_disease https://en.wikipedia.org/wiki/Apolipoprotein_E#Alzheimer's_d... Alz is not entirely dictated by genetics, but certain genetic alleles can influence your likelihood of developing the disease. I am watching my 81 year old mother go through this. She and I are both genetically predisposed. It's terrifying.
    - vimy 5y ago
      Look up the alzheimer’s is caused by pathogens hypothesis. If my parents start to develop alzheimer’s I will push for antivirals and antibiotics. Nothing to lose at that point. Edit: > The infectious hypothesis proposes that a pathogen (virus, bacteria, prion, etc.) is the root cause of AD [2]. The hypothesis is supported by evidence that some pathogens, such as herpesviruses and certain bacterial species, are found more commonly in AD patients. There is some variation within the infectious hypothesis field as to how an infectious pathogen explains the pathological hallmarks of AD. Direct infection and eventual death of central nervous system (CNS) cells by pathogens could explain the cognitive deficits and heightened inflammation found in AD [3]. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008596 https://journals.plos.org/plospathogens/article?id=10.1371/j...
      - alwillis 5y ago
        The gene coding for APOE exists in three frequent variants in humans: APOE2, present in 8% of the population, APOE3, the most common, and APOE4, which is found in nearly 15% of people and increases the risk of developing Alzheimer's disease by a factor of ten. https://medicalxpress.com/news/2022-03-role-lipids-alzheimer-disease.html https://medicalxpress.com/news/2022-03-role-lipids-alzheimer...
        vimy 5y ago
        This doesn't disprove the pathogen hypothesis. For example, having that gene could mean someone is less able to deal with infections.
        alwillis 5y ago
        Didn't suggest that it did but the most recent data suggests (in plain language) that brain cells forget how to be brain cells. They don't die; they begin excreting inflammatory substances and clog up the works. Researchers have tested in the lab on how to reset these cells or keep them from forgetting their identity in the first place. There's more data that suggests many diseases (including Alzheimer’s) are really the result of these cells losing their way. David Sinclair is the most eloquent that I've heard about this: https://youtu.be/n9IxomBusuw https://youtu.be/n9IxomBusuw
      - busyant 5y ago
        My mother participated in a clinical trial starting about 3 years ago. The rationale behind the investigational drug was that it might target inflammation associated with infection (I won't go into details). Honestly, I would have preferred a different trial, but this was the most reasonable one that was within driving distance of where she lives. The study was halted for futility. We also got a letter recently indicating that she was on placebo. Alz drug development is a graveyard so far.
    - kypro 5y ago
      Interestingly APOE4 is more common in African populations, although they have lower risk of developing Alzheimer's disease. My understanding is that there is a very large environmental role, and is possibly related to the poor diets and poor metabolic health of populations in Western countries. For example, diabetes has been associated with Alzheimer's disease.
      - p10_user 5y ago
        Both are diseases of degeneration. Degeneration accumulates from repeated stress. I wonder how many diseases are largely preventable if we were all more active and kept sugar consumption under control.
    - mleonhard 5y ago
      Have you read about albumin replacement therapy for Alzheimers? It's done well so far in human trials. https://pubmed.ncbi.nlm.nih.gov/25023458/ https://pubmed.ncbi.nlm.nih.gov/25023458/
  - novok 5y ago
    Things can be both. You have a genetic weakness to specific environmental insults that increase the probability you get alzheimer's for example. Another descriptor for alzheimer's is type 3 diabetes: https://en.wikipedia.org/wiki/Type_3_diabetes https://en.wikipedia.org/wiki/Type_3_diabetes
- airbreather 5y ago
  There's a standout anti inflammatory that is a turmeric extract. It is called circumin but is only effective when taken in the form with a pepper extract, pipinerol. But it is often sold in this combo. I have seen it have near miracle effects on soft tissue type injuries both personally and in others. Interestingly I know of medical practationers that take it prophalatically against alzeimers, not sure on what research they base their decision on, it might be speculative, but it seems to have zero harmful side effects that I can tell, so little chance of harm. So YMMV and DYOR, I'm not a doctor, just relating personal experience that might be helpful, but there is quite a lot of info out there if you care to research so just giving you something to think about and maybe try.
  - Brakenshire 5y ago
    I thought circumin combined with pepper was to increase bioavailability, which has since been found not to be useful because the effects occur in the gut, and don’t require absorption into the blood stream.
    - airbreather 5y ago
      You need the pipinerol, otherwise the effectiveness is greatly reduced. Probably why so many "studies" are inconclusive, apart from likely poorly structured.
  - TedDoesntTalk 5y ago
    The problem I’ve found is that a lot of turmeric and curcumin supplements or powders use heavy metals for orange coloring. Is there a brand you recommend?
    - m0llusk 5y ago
      Diaspora Company fair trade turmeric from Andhra Pradesh if you can get it. They have a number of channels that carry it through various spice distributors. Often sold as "single source" turmeric. Amazing quality quite unlike most other readily available turmeric. https://www.thebeaconsupply.com/product/diaspora-co-fair-trade-spices/3981 https://www.thebeaconsupply.com/product/diaspora-co-fair-tra...
abledon 5y ago
> uses pro-resolving lipid mediators to protect the brain from cognitive decline. These lipids are fatty acids, like omega-3, which are capable of easing inflammation. The ol' crazy monks seemed to be onto something in the Sushruta samhita, Volume II: "The term Nasya, in the specific sense, is particularly used with reference to the snuffing of any Sneha (oleaginous substance) with a view to make up the deficient oily matter in the brain in the case of a patient complaining of a sense of void or emptiness in the head or to impart tone to the nerves and muscles of the neck, shoulders and chest, or to invigorate the eye-sight."
lr4444lr 5y ago
A self-administered nasal spray is really gonna get appreciable amounts to the brain? I'm skeptical. Why not an infusion into the cerebrospinal fluid, or a topical ultrasound guided injection through a thinner, softer area of the skull?
- perrylaj 5y ago
  Yes, if it has the 'right' properties to pass through mucosa and the BBB, it's absolutely possible. How else would insufflated drugs like cocaine work? There are a number of nasal sprays that act on the CNS. Bupreborphine nasal spray is pretty common as a fast acting overdose treatment that also acts on the central nervous system.
petercooper 5y ago
It's interesting to see more associations between inflammation and dementia being acknowledged. My father was diagnosed with celiac disease in his late 50s but failed to adhere to the diet out of stubbornness. He suffered from much digestive pain (worth it, he said, to enjoy his much loved bread and ale) but over the course of a couple of years "independently" developed vascular dementia despite being mentally sharp (indeed, he was a C++ developer into his 60s) prior to this. (Long story short, he had a triple stroke in early 2021 and is now aphasic, living in a specialist care home, and seemingly lacks much connection to the world.) I've read some recent papers that begin to consider the possibility of inflammation caused by lack of adherence to medically necessary diets or allergic reactions leading to brain damage and vascular dementia, but it seems we're still a ways off mainstream medicine being in a position to use this as the basis of any advice for future patients. It's not very scientific of me, I admit, but I'm convinced there's a connection here, so my interest is piqued here.
jrapdx3 5y ago
No question Alzheimer's is a tragedy played out much too often. It's also a tremendously complex condition that's been the focus of research for decades. Inflammation contributes greatly to the disease burden of many conditions. Of course people vary in terms of inflammatory status. A moderate number of studies have shown omega-3 supplementation can reduce onset of some brain conditions, e.g., schizophrenia. In line with the mouse model it's well-accepted that inflammatory processes are implicated in AD. Microglial response triggers pro-inflammatory factors in turn leading to accumulation of toxic proteins in cortical neurons. Here's a succinct review of the subject: [0]. Anti-inflammatory agents have been associated preventative effects, e.g., NSAIDs though trials of these drugs haven't shown benefit. Omega-3 fatty acids have received a lot of study re: anti-inflammatory effects, particularly in cardiovascular disease. In AD some observational studies have shown reduction in risk of developing AD which is encouraging, however placebo-controlled studies have produced equivocal results, so the question remains open how much benefit omega-3 provides. This articles reviews the omega-3 evidence [1]. OTOH everyone seems to agree omega-3 intake through diet or supplementation will at least do no harm. On the whole diets higher in long-chain omega-3 fatty acids is likely to be most effective. Foods such as fish/seafood and green-leafy vegetables are good sources. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214864/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214864/ [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747747/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747747/
ncmncm 5y ago
I am interested in follow-up on recent-ish reports... One, in Taiwan, showing a strong effect of treatment for herpes reducing incidence of Alzheimers Another, reported last year in Kansas City, a six-year study of tens of thousands of Veterans Administration patients over 70 showing that a recent Tdap vaccination predicts a 40% reduction in dementia diagnoses, replicated in another large, independent cohort. You don't need a very good reason to get a Tdap booster. Or even a prescription.
chrismeller 5y ago
I got excited thinking all these decades of suffering through allergies were finally going to pay off…

114 points by happyopossum 5y ago

donkeydoug 5y ago

.... in mice.

rzzzt 5y ago
Indeed, from the LSU Health announcement: "The study uses the AppNL-G-F/NL-G-F mouse model for AD."

Damogran6 5y ago

Wife has a genetic predisposition towards Alzheimer's...All of these articles both fill me with hope and dread at the same time. We watched her Father and Grandfather succumb and I'm so hopeful something will be found and come to bear in time to help her if she needs it.

jjtheblunt 5y ago
how do they know it's genetic and not environmental?
- busyant 5y ago
  https://en.wikipedia.org/wiki/Apolipoprotein_E#Alzheimer's_disease https://en.wikipedia.org/wiki/Apolipoprotein_E#Alzheimer's_d... Alz is not entirely dictated by genetics, but certain genetic alleles can influence your likelihood of developing the disease. I am watching my 81 year old mother go through this. She and I are both genetically predisposed. It's terrifying.
  - vimy 5y ago
    Look up the alzheimer’s is caused by pathogens hypothesis. If my parents start to develop alzheimer’s I will push for antivirals and antibiotics. Nothing to lose at that point. Edit: > The infectious hypothesis proposes that a pathogen (virus, bacteria, prion, etc.) is the root cause of AD [2]. The hypothesis is supported by evidence that some pathogens, such as herpesviruses and certain bacterial species, are found more commonly in AD patients. There is some variation within the infectious hypothesis field as to how an infectious pathogen explains the pathological hallmarks of AD. Direct infection and eventual death of central nervous system (CNS) cells by pathogens could explain the cognitive deficits and heightened inflammation found in AD [3]. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008596 https://journals.plos.org/plospathogens/article?id=10.1371/j...
    - alwillis 5y ago
      The gene coding for APOE exists in three frequent variants in humans: APOE2, present in 8% of the population, APOE3, the most common, and APOE4, which is found in nearly 15% of people and increases the risk of developing Alzheimer's disease by a factor of ten. https://medicalxpress.com/news/2022-03-role-lipids-alzheimer-disease.html https://medicalxpress.com/news/2022-03-role-lipids-alzheimer...
      - vimy 5y ago
        This doesn't disprove the pathogen hypothesis. For example, having that gene could mean someone is less able to deal with infections.
        alwillis 5y ago
        Didn't suggest that it did but the most recent data suggests (in plain language) that brain cells forget how to be brain cells. They don't die; they begin excreting inflammatory substances and clog up the works. Researchers have tested in the lab on how to reset these cells or keep them from forgetting their identity in the first place. There's more data that suggests many diseases (including Alzheimer’s) are really the result of these cells losing their way. David Sinclair is the most eloquent that I've heard about this: https://youtu.be/n9IxomBusuw https://youtu.be/n9IxomBusuw
    - busyant 5y ago
      My mother participated in a clinical trial starting about 3 years ago. The rationale behind the investigational drug was that it might target inflammation associated with infection (I won't go into details). Honestly, I would have preferred a different trial, but this was the most reasonable one that was within driving distance of where she lives. The study was halted for futility. We also got a letter recently indicating that she was on placebo. Alz drug development is a graveyard so far.
  - kypro 5y ago
    Interestingly APOE4 is more common in African populations, although they have lower risk of developing Alzheimer's disease. My understanding is that there is a very large environmental role, and is possibly related to the poor diets and poor metabolic health of populations in Western countries. For example, diabetes has been associated with Alzheimer's disease.
    - p10_user 5y ago
      Both are diseases of degeneration. Degeneration accumulates from repeated stress. I wonder how many diseases are largely preventable if we were all more active and kept sugar consumption under control.
  - mleonhard 5y ago
    Have you read about albumin replacement therapy for Alzheimers? It's done well so far in human trials. https://pubmed.ncbi.nlm.nih.gov/25023458/ https://pubmed.ncbi.nlm.nih.gov/25023458/
- novok 5y ago
  Things can be both. You have a genetic weakness to specific environmental insults that increase the probability you get alzheimer's for example. Another descriptor for alzheimer's is type 3 diabetes: https://en.wikipedia.org/wiki/Type_3_diabetes https://en.wikipedia.org/wiki/Type_3_diabetes
airbreather 5y ago
There's a standout anti inflammatory that is a turmeric extract. It is called circumin but is only effective when taken in the form with a pepper extract, pipinerol. But it is often sold in this combo. I have seen it have near miracle effects on soft tissue type injuries both personally and in others. Interestingly I know of medical practationers that take it prophalatically against alzeimers, not sure on what research they base their decision on, it might be speculative, but it seems to have zero harmful side effects that I can tell, so little chance of harm. So YMMV and DYOR, I'm not a doctor, just relating personal experience that might be helpful, but there is quite a lot of info out there if you care to research so just giving you something to think about and maybe try.
- Brakenshire 5y ago
  I thought circumin combined with pepper was to increase bioavailability, which has since been found not to be useful because the effects occur in the gut, and don’t require absorption into the blood stream.
  - airbreather 5y ago
    You need the pipinerol, otherwise the effectiveness is greatly reduced. Probably why so many "studies" are inconclusive, apart from likely poorly structured.
- TedDoesntTalk 5y ago
  The problem I’ve found is that a lot of turmeric and curcumin supplements or powders use heavy metals for orange coloring. Is there a brand you recommend?
  - m0llusk 5y ago
    Diaspora Company fair trade turmeric from Andhra Pradesh if you can get it. They have a number of channels that carry it through various spice distributors. Often sold as "single source" turmeric. Amazing quality quite unlike most other readily available turmeric. https://www.thebeaconsupply.com/product/diaspora-co-fair-trade-spices/3981 https://www.thebeaconsupply.com/product/diaspora-co-fair-tra...

abledon 5y ago

> uses pro-resolving lipid mediators to protect the brain from cognitive decline. These lipids are fatty acids, like omega-3, which are capable of easing inflammation. The ol' crazy monks seemed to be onto something in the Sushruta samhita, Volume II: "The term Nasya, in the specific sense, is particularly used with reference to the snuffing of any Sneha (oleaginous substance) with a view to make up the deficient oily matter in the brain in the case of a patient complaining of a sense of void or emptiness in the head or to impart tone to the nerves and muscles of the neck, shoulders and chest, or to invigorate the eye-sight."

lr4444lr 5y ago

A self-administered nasal spray is really gonna get appreciable amounts to the brain? I'm skeptical. Why not an infusion into the cerebrospinal fluid, or a topical ultrasound guided injection through a thinner, softer area of the skull?

perrylaj 5y ago
Yes, if it has the 'right' properties to pass through mucosa and the BBB, it's absolutely possible. How else would insufflated drugs like cocaine work? There are a number of nasal sprays that act on the CNS. Bupreborphine nasal spray is pretty common as a fast acting overdose treatment that also acts on the central nervous system.

petercooper 5y ago

It's interesting to see more associations between inflammation and dementia being acknowledged. My father was diagnosed with celiac disease in his late 50s but failed to adhere to the diet out of stubbornness. He suffered from much digestive pain (worth it, he said, to enjoy his much loved bread and ale) but over the course of a couple of years "independently" developed vascular dementia despite being mentally sharp (indeed, he was a C++ developer into his 60s) prior to this. (Long story short, he had a triple stroke in early 2021 and is now aphasic, living in a specialist care home, and seemingly lacks much connection to the world.) I've read some recent papers that begin to consider the possibility of inflammation caused by lack of adherence to medically necessary diets or allergic reactions leading to brain damage and vascular dementia, but it seems we're still a ways off mainstream medicine being in a position to use this as the basis of any advice for future patients. It's not very scientific of me, I admit, but I'm convinced there's a connection here, so my interest is piqued here.

jrapdx3 5y ago

No question Alzheimer's is a tragedy played out much too often. It's also a tremendously complex condition that's been the focus of research for decades. Inflammation contributes greatly to the disease burden of many conditions. Of course people vary in terms of inflammatory status. A moderate number of studies have shown omega-3 supplementation can reduce onset of some brain conditions, e.g., schizophrenia. In line with the mouse model it's well-accepted that inflammatory processes are implicated in AD. Microglial response triggers pro-inflammatory factors in turn leading to accumulation of toxic proteins in cortical neurons. Here's a succinct review of the subject: [0]. Anti-inflammatory agents have been associated preventative effects, e.g., NSAIDs though trials of these drugs haven't shown benefit. Omega-3 fatty acids have received a lot of study re: anti-inflammatory effects, particularly in cardiovascular disease. In AD some observational studies have shown reduction in risk of developing AD which is encouraging, however placebo-controlled studies have produced equivocal results, so the question remains open how much benefit omega-3 provides. This articles reviews the omega-3 evidence [1]. OTOH everyone seems to agree omega-3 intake through diet or supplementation will at least do no harm. On the whole diets higher in long-chain omega-3 fatty acids is likely to be most effective. Foods such as fish/seafood and green-leafy vegetables are good sources. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214864/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214864/ [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747747/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747747/

ncmncm 5y ago

I am interested in follow-up on recent-ish reports... One, in Taiwan, showing a strong effect of treatment for herpes reducing incidence of Alzheimers Another, reported last year in Kansas City, a six-year study of tens of thousands of Veterans Administration patients over 70 showing that a recent Tdap vaccination predicts a 40% reduction in dementia diagnoses, replicated in another large, independent cohort. You don't need a very good reason to get a Tdap booster. Or even a prescription.

chrismeller 5y ago

I got excited thinking all these decades of suffering through allergies were finally going to pay off…