14 ms·
Root cause of Alzheimer's may be fat buildup in brain cells, research suggests
- FrustratedMonky 3y agoSo, is this why fasting sometimes seems like a solution? Edit: Oversimplified, but: Less, calories, less fat? Excess calories, more fat?
- resource_waste 3y agoYou should word this better. But I think Fasting helps because of autophagy, I don't think these are exactly related. I thought autophagy takes out proteins too.
- spudlyo 3y agoFasting seems like a solution because in the fasted state your body doesn't need to produce insulin. Your body needs insulin to push fat into cells. Your pancreas gets a break, and perhaps sensitivity improves when you go on an extended insulin-free holiday.
- ajross 3y agoExcept there's literally a result out this week linking fasting (specifically 16+ hour intermittent fasting) with a 91% increase in cardiovascular disease deaths, which if it holds up would utterly swamp any incremental improvements to alzheimers risk. No free lunch in personal health decisions, alas. Really the only good advice is stick to well-established science, be healthy in general, avoid internet advice, and don't sweat the small stuff.
- freddie_mercury 3y agoThe results unfortunately are too vague to support that interpretation. There was no causal linkage because they couldn't determine why people were fasting: suppressed appetite due to illness, suppressed appetite due to being a smoker (which is very common), skipping meals due to poverty. It also found that while cardiovascular deaths increased by 91% overall deaths were completely unchanged...which is a bit difficult to reconcile.
- ajross 3y ago> The results unfortunately are too vague to support that interpretation. I think you completely missed the point. Sure, it's a new result and being an outlier needs to be treated with care (which I believe I said). It's still a more rigorous finding of health effect than anything in the grandparent's comment about how you should fast to avoid Alzheimer's. Ergo advice like that is bad.
- FrustratedMonky 3y agoThank You It seems counterintuitive, and opposite of what is promoted. I'll have to check it out more. But from AHA, this is enough of a dramatic result to at least follow up on. 8-hour time-restricted eating linked to a 91% higher risk of cardiovascular death https://newsroom.heart.org/news/8-hour-time-restricted-eating-linked-to-a-91-higher-risk-of-cardiovascular-death https://newsroom.heart.org/news/8-hour-time-restricted-eatin...
- joshuahaglund 3y agoI'm no biologist but it's my understanding that insulin causes cells take up glucose, not fats. And I don't see anyone suggesting insulin or the pancreas is involved in any of this. So what does the pancreas have to do with Alzheimers?
- GeoAtreides 3y ago> I don't see anyone suggesting Have you looked? "Although many factors affect fat cells, the hormone insulin exerts dominant anabolic control. Insulin decreases the circulating concentration of all major metabolic fuels by stimulating glucose uptake into tissues, suppressing release of fatty acids from adipose tissue, inhibiting production of ketones in the liver, and promoting fat and glycogen deposition." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082688/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082688/ Or this one: https://www.nih.gov/news-events/news-releases/nih-study-shows-how-insulin-stimulates-fat-cells-take-glucose https://www.nih.gov/news-events/news-releases/nih-study-show... There are many many other studies and articles, as the insulin-fat storage connection is very well documented
- spudlyo 3y agoIt depends what cells we're talking about. Thanks to insulin, glucose can be stored in the liver and muscle tissues as glycogen. In folks with poor insulin sensitivity these cells do not respond as effectively to insulin, and their uptake and storage is reduced, leaving more glucose in the bloodstream. In the obese, it's also likely the liver and muscle tissue glycogen stores are near max capacity. In this case insulin facilitates the uptake of glucose into adipose (fat) tissue through a process known as lipogenesis. When I wrote "insulin pushes fat into cells" that's what I meant.
- crakenzak 3y agoThe insulin protein promotes glucose (not fats) uptake into the muscles (~75%), liver (~15%), and other tissue (~10%) to aggressively lower blood sugar levels back to a total circulating amount of ~5g.
- spudlyo 3y agoIn the obese, glucose is preferentially directed to adipose tissue for storage as fat. This is due to both insulin resistance, and to the limited storage capacity in muscles and the liver for glucose in the form of glycogen. I was writing colloquially and intentionally left out details like lipogenesis, which in retrospect probably wasn't a great idea.
- deleted 3y ago[deleted]
- superbiome 3y agoIn addition to weight loss, fasting can reduce activated microglia in the brain which could play some part in this, as microglia was mentioned in the study.
- pama 3y agoAs per the Nature paper, this is an immune system mechanism with these particular “fat” particles presumed to help fend off an invading microbe. So no, it doesn’t matter how much fat or not you have to begin with as you cannot as easily reduce the immune system ability to do its work, and even if you did somehow manage to stop this particular immune response it is far from clear if you would get more or less dementia as a result.
- bananapub 3y agotl;dr no one knows, lots of hints but every attempt at chemical intervention turns out to be worthless
- armadsen 3y agoThe latest approved Alzheimer’s drug, Lecanemab, shows a cognitive benefit. It’s modest, but there are already successors in the pipeline that have shown promise (e.g. donanemab). They’re baby steps, not at all cures, and have significant side effects, but “everything we try doesn’t work at all” isn’t really true the way it was even a few years ago.
- nottorp 3y agoAs with everything else unknown, no one knows yet. Remember that only 100 years ago you could die from an infection.
- julienchastang 3y agoI suggest changing the title to something like: "Link Between Brain Cell Fat and Alzheimer’s Could Pave the Way for Innovative Treatments". Also here is the original Nature journal reference that can be linked to instead: https://www.nature.com/articles/s41586-024-07185-7 https://www.nature.com/articles/s41586-024-07185-7
- david-gpu 3y agoDoesn't this boost the hypothesis that Alzheimer's is closely related to insulin resistance in the brain? What some people call type III diabetes. I ask because one of the hallmarks of insulin resistance is the presence of lipid droplets in close proximity to mitochondria [0]. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455923/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10455923/
- echelon 3y agoHere's what the authors speculate [1], > A recent report showed that innate immune triggers (for example, Escherichia coli and Salmonella) induce LD formation in peripheral macrophages as part of an evolutionarily conserved antimicrobial defence in which LDs coated with antimicrobial proteins, such as cathelicidin (CAMP), kill bacteria8. We speculate that a similar programme can be triggered in human microglia exposed to Aβ, LPS and other innate immune activators and disrupt brain homeostasis. Protein aggregates found in other neurodegenerative diseases may trigger the LDAM state. For example, alpha-synuclein binding to TLR2 and TLR5 induces microglial NLRP3 inflammasome activation, which is a shared signature seen in LDAM36. Given that we recently identified that LDAM are abundant in the ageing mouse brain, LDAMs may also be triggered by hitherto unknown protein aggregates and innate immune activators which accumulate with age. Interestingly, the most enriched pathway in human LD-containing iMGs is ‘cellular senescence’, similar to lipid-laden ‘foamy macrophages’ in atherosclerosis which have a senescent phenotype and are drivers of pathology37. Perhaps in the natural ageing of various organs, LD-accumulating tissue-resident macrophages represent a general class of senescent myeloid cells which are drivers of tissue inflammation. It could be a lot of things, and there might be multiple pathways that lead to this state. [1] https://www.nature.com/articles/s41586-024-07185-7#Sec6 https://www.nature.com/articles/s41586-024-07185-7#Sec6
- m463 3y agosleep problems (like sleep apnea) affect insulin resistance and weight gain. This goes with other evidence that not sleeping correlates with alzheimers. So the fat buildup correlates in a different way.
- levocardia 3y agoThere's a really interesting paradox where, compared to healthy adults, intramuscular lipid droplet storage near mitochondria is increased in: 1) People with obesity 2) People with type 2 diabetes 3) People who do endurance exercise Even though #3 is highly protective against #1 and #2. The best explanation I've seen is that the important difference is why the lipid droplets are being deposited [1] [1] https://link.springer.com/article/10.1007/s00424-005-1509-0 https://link.springer.com/article/10.1007/s00424-005-1509-0
- deleted 3y ago[deleted]
- atum47 3y agoMy aunt started showing symptoms of Alzheimer's. My grandfather passed from it. Is there any thing to do in order to prevent or delay the disease?
- delichon 3y ago[flagged]
- mike_d 3y agoAs the study points out, we don't even know the mechanism that causes Alzheimer's. Anyone claiming to be able to sway your odds one way or the other is flat out lying because they don't know either. She is a media personality first and foremost, peddling a book, speaking circuit, private trainings, etc for her fad diet. As for her credentials, remember Dr. Oz was a doctor too before he saw dollar signs. Here are some good resources for you to check out: https://consumer.ftc.gov/articles/common-health-scams https://consumer.ftc.gov/articles/common-health-scams https://www.healthychildren.org/English/family-life/Media/Pages/Medicine-Ads.aspx https://www.healthychildren.org/English/family-life/Media/Pa... https://www.nytimes.com/2023/05/10/well/move/fitness-influencers.html https://www.nytimes.com/2023/05/10/well/move/fitness-influen...
- gverri 3y agoFirst it would be good to know if you have genetic predisposition. I think mosts comercial DNA tests available test for APOE4 variations. Second I would read on the research of Dr. Dale Bredesen. He has been studying how to map all the underlying factors that can lead to Alzheimer and how to test/treat markers that are associated with the disease. According to him Alzheimer's disease is like a roof full of holes. You need to test and treat each individual hole to make sure it's not leaking.
- armadsen 3y agoThis is good advice. Be aware that while APOE variants are the most well known and common causes of a genetic predisposition to Alzheimer’s, there are several others, including some 100% penetrance, dominant gene mutations that cause it. Unfortunately I have very significant experience with one of these. Generally it would be common enough in your family (roughly 50% of people getting it), that you’d have reason to suspect one of these gene mutations.
- patrickhogan1 3y ago+1 for GLP1
- copperx 3y agoDo GLP1 agents go through the brain blood barrier?
- stewpy 3y agothey could help prevent the occurrence
- patrickhogan1 3y agoGLP1 analogs can cross the blood–brain barrier and stimulate the GLP1 receptor in the brain.[1] There is also research showing improvement in Alzheimer's disease symptoms. [2] [1] https://pubmed.ncbi.nlm.nih.gov/11931352/ https://pubmed.ncbi.nlm.nih.gov/11931352/ [2] https://www.sciencedirect.com/science/article/pii/S221287782100020X https://www.sciencedirect.com/science/article/pii/S221287782...
- Integrape 3y agoI hope you're right
- Solvency 3y agoPaul Saladino has been saying this for over 5 years but people ignore him because he's often shirtless and eats lots of protein.
- Hydraulix989 3y agoA broken clock is right two times a day.
- jfray2k22 3y agoA stopped clock is right twice a day. A broken clock could potentially never be right, like if it's perpetually 10 minutes behind.
- tmtvl 3y agoThat's not a broken clock, that's a clock that's set to the wrong time. Unless it remains 10 minutes behind, even when you set it 10 minutes forward, which would be a great prank gift.
- foobar1962 3y agoA broken analogy never stops.
- deleted 3y ago[deleted]
- yosito 3y agoPaul Saladino says a lot of things. Which of his claims are you specifically referencing here?
- Solvency 3y agoAbout fat accumulation and decades of chronic inflammation in the brain being huge factors for Alzheimer's.
- patel011393 3y agoBe careful interpreting this study summary. The article's peer reviews (on PubPeer) list a few analytic issues that call the findings into question: https://pubpeer.com/publications/59F515775D10D854ABB7F4B31D445B?utm_source=Chrome&utm_medium=BrowserExtension&utm_campaign=Chrome https://pubpeer.com/publications/59F515775D10D854ABB7F4B31D4...
- irjustin 3y agoHrmmmmm the controls for the first 2 graphs appear to be the same and they're called out for it [0]. But it could very well be that they're supposed to be the same? Authors may just need to better highlight why the same control is allowed to be use for comparing 2 different result sets. [0] https://pubpeer.com/publications/59F515775D10D854ABB7F4B31D445B#4 https://pubpeer.com/publications/59F515775D10D854ABB7F4B31D4...
- patel011393 3y agoYep, but other issues are discussed too. Suspicion is warranted, though signs of errors and fraud require even deeper investigation.
- ProjectArcturis 3y agoAs a former Alzheimer's researcher, this is a big fucking deal. It puts together a lot of clues (APOE risk, microglia) and finds a theory that makes a lot of sense. All around the world, there are labs pulling late nights trying to figure out how to drug this.
- yosito 3y agoAre you aware of any other studies that support this theory? In other words, is this replicable?
- ianai 3y agoWhat kind of fat is it? Like is it possible to avoid by avoiding too much fat?
- Turskarama 3y agoToo early to know for sure but I'm going to say it's very unlikely, the relationship between diet and body composition is rarely so straight forward.
- rustcleaner 3y ago[flagged]
- deleted 3y ago[deleted]
- water-data-dude 3y agoThat seems like a needlessly bitter response, why the antipathy?
- Cornbilly 3y agoThere is a weird crowd of people on the internet that have convinced themselves that seed oils are the cause of many ailments. It doesn’t have a ton of scientific backing but Joe Rogan promoted some guru doctor a while back that spread the idea to a lot more people.
- patrickhogan1 3y agoGLP1 analogs could help. They can cross the blood–brain barrier and stimulate the GLP1 receptor in the brain.[1] There is also research showing improvement in Alzheimer's disease symptoms. [2] [1] https://pubmed.ncbi.nlm.nih.gov/11931352/ https://pubmed.ncbi.nlm.nih.gov/11931352/ [2] https://www.sciencedirect.com/science/article/pii/S221287782100020X https://www.sciencedirect.com/science/article/pii/S221287782...
- arcticbull 3y agoGLP-1s definitely cross the blood-brain barrier - work by affecting the GABAergic CNS and making you not hungry so you stop eating and lose weight. They don't independently do anything to make you slimmer. Basically what you're suggesting is people lose weight, which, I agree.
- datavirtue 3y ago[flagged]
- huppeldepup 3y agoIs this correlated with obesity demographics, i.e. Japan/US/EU statistics? I can’t find reliable numbers per country, most sources conflate the different types into dementia.
- idontknowabout 3y agoChatGPT already knows all this so it must be old news
- ethn 3y agoFatty cell infiltration occurs when the stem cell niches don't fully convert into its end cell both Glia and Neuron. This would then indicate that TZDs can be effective in promoting the correct differentiation
- deleted 3y ago[deleted]
- deterministic 3y agoAnother theory is that Alzheimer's is caused by the brain becoming insulin resistant. Some researchers even argue that Alzheimer's should be called type 3 diabetes.