Nasal spray could prevent Alzheimer’s disease, brain inflammation | Hacker News Reader

Nasal spray could prevent Alzheimer’s disease, brain inflammation

braintomorrow.com

114 pointshappyopossum35 comments

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.

how do they know it's genetic and not environmental?

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.

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/j...

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...

This doesn't disprove the pathogen hypothesis. For example, having that gene could mean someone is less able to deal with infections.

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

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.

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.

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.

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/

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

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.

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.

You need the pipinerol, otherwise the effectiveness is greatly reduced.

Probably why so many "studies" are inconclusive, apart from likely poorly structured.

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?

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-tra...

Buy whole turmeric from a local Indian grocery and powder it yourself? Curcumin is about 1-3% by weight in turmeric.

I did look into this before and it seemed like yes, curcumin is effective if it can get into the gut, but also it's mostly destroyed by stomach acid so you need to either take huge amounts or take specially prepared capsules that will release the curcumin in the intestine.

I'm not a doctor and I didn't follow up on this for a few years. But it's something to consider if you plan to take this - just eating loads of turmeric is probably not going to do anything (although it's tasty and probably has other health benefits not related to curcumin).

According to wikipedia: «Although curcumin has been assessed in numerous laboratory and clinical studies, it has no medical uses established by well-designed clinical research. According to a 2017 review of more than 120 studies, curcumin has not been successful in any clinical trial, leading the authors to conclude that "curcumin is an unstable, reactive, non-bioavailable compound and, therefore, a highly improbable lead".»

Not sure how accurate or up to date this wikipedia page is, though.

> Not sure how accurate or up to date this wikipedia page is, though.

Wikipedia is probably the last place I would check for scientific information.

Why is that?

Wikipedia isn't the source of the scientific information -- as is immediately apparent from the quoted sentence -- and I think basic media literacy requires that you not participate in the conversation if you can't parse that from the quote.

The sources are this expensive review: https://pubs.acs.org/doi/10.1021/acs.jmedchem.6b00975

And this related letter by the authors summarizing the review: https://pubs.acs.org/doi/10.1021/acsmedchemlett.7b00139

High impact factor journal, at a basic scan the quote is accurate to the article, and the article uses standard methods. Authors all seem appropriately credentialled and working out of real institutions. Article itself has a high record of citation, and the constituent studies are all properly cited for you to proceed.

Examine has a summary of the research which provides some reason for optimism:

https://examine.com/supplements/curcumin/

It seems plausible that there could be something going on here, but as with most supplements there's not nearly enough data yet.

I'd suggest that the "miraculous" effects the parent describes would more likely be attributed to placebo, though. These things tend to work around the margins, not with dramatic improvements, which is why they're hard to study.

The problem here is that there’s lots of eyes on the problem, not all of them qualified, and there isn’t a body of work to lean on. Amyloid plaque removal was a strong contender for a bit, and there’s thinking that near 100% memory recovery will be possible when the root cause is addressed, and there’s a TON of attention in the space, but we’re not there yet.

Total BS, not placebo, I don't take shit if it doesn't have an impact that I can notice. I've been thru this before, studies this, studies that, you know, just try it, if it doesn't work for you don't continue. I just put my locksmith onto it today, he came around with his hand all swollen up, said he felt something go snap in it yesterday. I gave him 3 with a glass of milk and 20 minutes later he was already noticing improvement. Apparently it works by blocking the the inflammatory chemicals the body sends to an injury, but I'm just an electrical engineer so don't take anything I say about biochemistry seriously.

Brand I like is Bioglan, double strength. I have put maybe 30 people onto it that have all had positive effects.

A few years ago we went to Ulawatu in Bali and the chalet owner there was an old American guy Rob who had a disk injury from surfing years ago that flared up now and then and he was on some serious prescription anti-inflammatories, but they rendered him with serious cognitive difficulties. We have him some Curcumin and he said within the hour he could feel the pressure come off. When we left a few days later his Balinese wife was literally prostrate on the ground clutching feet and weeping with tears of thanks and appreciation. So if that's placebo, I'll take it anyway, but it's not.

Sick of armchair experts that read a bunch of poorly execute studies and start spouting off claims, but never actually try it. The chances of harm are very low , and you might be surprised how effective it is because my experience, and that of many others, is that it beats anything prescription, for certain injuries, hands f$cking down.

Placebo my arse.

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.

> 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."

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/ [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747747/

.... in mice.

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

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?

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.

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.

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

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