[HN Gopher] New research links potentially toxic fat-protein com...
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New research links potentially toxic fat-protein complexes to
Alzheimer's
Author : echelon
Score : 89 points
Date : 2021-11-30 16:33 UTC (6 hours ago)
(HTM) web link (www.medicalnewstoday.com)
(TXT) w3m dump (www.medicalnewstoday.com)
| HappySweeney wrote:
| For those of us genetically predisposed to this disease, what
| dietary changes would theoretically result in a reduction of
| risk?
| Gatsky wrote:
| One option is to eat less of everything. This may sound dumb
| but in the current stone age understanding of nutrition and
| health, it is a reasonable option.
|
| The only foods which are 'definitely safe' are leafy greens and
| cruciferous vegetables. Could probably add berries to that in
| moderation. Not saying that is all one should eat, what I mean
| is to eat less of everything else than baseline, to some
| caloric deficit. This excludes the few people who are
| underweight for whatever reason, and those with certain
| diseases.
| ransom1538 wrote:
| "leafy greens and cruciferous vegetables" Aren't these
| covered in pesticides? If you are looking for reasons to not
| eat: https://www.nytimes.com/2006/10/31/health/nutrition/31ag
| in.h...
|
| https://www.kxan.com/news/simplehealth/dirty-dozen-which-
| fru...
| pawelmurias wrote:
| If you where in a constant state of caloric deficit you would
| constantly loose weight.
| JimTheMan wrote:
| At every calorie level above starvation, there is an
| equilibrium weight associated.
|
| (Metabolism (which drops with less weight) + Exercise -
| Intake) -> over time -> equilibrium weight.
|
| So assuming you pick a low calorie diet for now, eventually
| you'd maintain at a skinny weight.. and maybe live longer.
| Maybe.
| dilyevsky wrote:
| Coffee and exercise have been shown to have protective effect
| (not sure how robust those studies are) which seems consistent
| with liver health/fat metabolism action...
| mrec wrote:
| Do you know if it's the caffeine in coffee, or something
| else? (i.e. does decaf work?)
| discreteevent wrote:
| Also nicotine.
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1670208/
| Fordec wrote:
| What seems to be hinted at through this and other research out
| in the past 12 month:
|
| Reduce fat intake.
|
| It's not the cause, but the carrier of toxins across the blood-
| brain carrier. Reducing fat would reduce the rate of toxin
| build up. It's not a cure, nor does it tackle the genetic
| component, but way to prolong lifestyle.
| dralley wrote:
| Bad news for the Keto dieters.
| humps wrote:
| I don't think that fits. Someone following a strict keto or
| low-carb diet is typically going to have healthier levels
| of fat in their blood e.g. lower cholesterol. Add to that a
| greatly reduced risk of diabetes and if these findings
| prove true it may end up being another reason to adopt such
| a diet.
| notshift wrote:
| Not sure what evidence you've been looking at; from what I've
| read the opposite is true: Keto diet can be an effective
| treatment for Alzheimer's.
|
| https://m.youtube.com/watch?v=jK6-r1zWOI0
| ajaxowl wrote:
| There are many dietary changes that can be implemented to
| decrease the odds of the disease occurring in those who are
| genetically predisposed. Look into a nutrition program that
| specializes in Alzheimer's prevention.
|
| For example: https://amosinstitute.com/cognitive-health-
| program/
| hadlock wrote:
| I am not a liver expert, but it seems like those kinds of
| compounds might be created by a malfunctioning liver, rather
| than specifically diet induced.
| abfan1127 wrote:
| why is the liver malfunctioning? perhaps its a malfunction
| induced by diet?
| echelon wrote:
| It's hard to say right now. It might be one possibility if this
| line of research pans out.
|
| This is a potential mechanism that they've experimentally built
| and triggered. There's no guarantee this happens _in situ_
| exactly as they 've set up. There's also the chance that
| Alzheimer's is caused by various contributing factors.
|
| This paper does look promising though, because they've
| triggered the disease from the liver using lipoproteins that
| have been observed.
|
| I'd love for domain experts to weigh in.
| victorvosk wrote:
| It doesn't seem like they draw any correlation to food intake
| since the mice were genetically modified to just emit the
| proteins from their livers.
|
| My guess is healthy diet and exercise go a long way. Don't
| drink and avoid sugar (diabetes) both of which are damaging to
| the liver.
| rafaelero wrote:
| Minimally processed plant-based diets. People keep fighting it,
| but it always comes back as the optimal diet to healhty
| longevity.
| xdrone wrote:
| some would say saturated fat is the cause
|
| the mechanism could be atherosclerosis
| https://youtu.be/t-noCw4LsY4?t=168
|
| linear correlation by country https://youtu.be/Gel4vlG4Jbk?t=68
|
| personally, i think something close to wfpb diet is the best
| for all things (except gaining weight).
| [deleted]
| echelon wrote:
| (Reposting again since it wasn't noticed ~1.5 months ago.)
|
| This paper looks really good.
|
| Amyloid beta has long been implicated in Alzheimer's. Now they've
| found a way to trigger the disease by generating amyloid in the
| liver and shown that it can reach the brain (by crossing the
| blood brain barrier). This setup was shown to trigger the
| disease. It's a very plausible mechanism that worked end-to-end
| and seems to fit all of the observational evidence we've
| gathered.
|
| The paper: Synthesis of human amyloid restricted to liver results
| in an Alzheimer disease-like neurodegenerative phenotype
|
| https://journals.plos.org/plosbiology/article?id=10.1371/jou...
|
| Abstract:
|
| > Several lines of study suggest that peripheral metabolism of
| amyloid beta (Ass) is associated with risk for Alzheimer disease
| (AD). In blood, greater than 90% of Ass is complexed as an
| apolipoprotein, raising the possibility of a lipoprotein-mediated
| axis for AD risk. In this study, we report that genetic
| modification of C57BL/6J mice engineered to synthesise human Ass
| only in liver (hepatocyte-specific human amyloid (HSHA) strain)
| has marked neurodegeneration concomitant with capillary
| dysfunction, parenchymal extravasation of lipoprotein-Ass, and
| neurovascular inflammation. Moreover, the HSHA mice showed
| impaired performance in the passive avoidance test, suggesting
| impairment in hippocampal-dependent learning. Transmission
| electron microscopy shows marked neurovascular disruption in HSHA
| mice. This study provides causal evidence of a lipoprotein-Ass
| /capillary axis for onset and progression of a neurodegenerative
| process.
|
| We knew amyloid beta was highly associated with Alzheimer's.
| We've been studying this for decades.
|
| The researchers noticed amyloid beta was found in lipoprotein
| complexes (fat+protein), then experimentally modified the liver
| to produce it. The protein leaks out of the liver and causes
| neurodegeneration.
|
| > Insight into how blood Ab increases risk for AD comes from
| findings that in humans, greater than 90% of blood Ab1-40 and 97%
| of the particularly pro-amyloidogenic Ab1-42 is associated with
| plasma lipoproteins [3], principally the triglyceride-rich
| lipoproteins (TRLs) of hepatically derived very low-density
| lipoproteins (VLDLs) and of postprandial chylomicrons [4,5].
| Direct evidence of a peripheral TRL-Ab/vascular risk pathway for
| AD comes from studies in preclinical models, which show that
| cerebral capillary amyloid-angiopathy, a common early
| neurovascular pathology of AD, may be a consequence of
| parenchymal extravasation of TRL-Ab.
|
| This implicates fatty acids originating from the liver migrating
| (extravasation). And they just experimentally reproduced this.
|
| Some quotes from the linked article:
|
| > "This study," he added, "shows that exaggerated abundance in
| blood of potentially toxic fat-protein complexes can damage
| microscopic brain blood vessels called capillaries and,
| thereafter, leak into the brain, causing inflammation and brain
| cell death."
|
| > "[Changes] in dietary behaviors and certain medications could
| potentially reduce blood concentration of these toxic fat-protein
| complexes, [subsequently] reducing the risk for Alzheimer's or
| [slowing] down the disease progression," he concluded.
|
| This would suggest that liver health and diet can play a factor
| in disease development.
|
| Of course there's the chance that this is just a really good
| "biologically plausible" mechanism that looks good on paper, but
| might not naturally occur outside of this experimental setup.
| There will need to be much more research to either prove or rule
| this out.
|
| This looks exciting though.
| newsbinator wrote:
| > [Changes] in dietary behaviors and certain medications could
| potentially reduce blood concentration of these toxic fat-
| protein complexes, [subsequently] reducing the risk for
| Alzheimer's
|
| What would be some recommended changes in dietary behaviors if
| this link were also verified in humans?
| notshift wrote:
| There have been several studies done showing that a healthy
| keto diet can reduce or even reverse Alzheimers symptoms in
| many patients. Just do a quick Google or YouTube search, lots
| of content on the subject.
| monopoledance wrote:
| Not exactly what they hint at in this study...
|
| > In wild-type (WT) C57BL/6J mice, a saturated fatty acid
| (SFA)-enriched diet was found to strongly stimulate
| biosynthesis and secretion of TRL-Ab, concomitant with a
| reduction in cerebral capillary endothelial tight junction
| proteins, blood-to-brain extravasation of TRL-Ab, and
| marked neurovascular inflammation [6]. In contrast, mice
| fed unsaturated fatty acid-rich diets had no evidence of
| exaggerated TRL-Ab secretion and capillary integrity was
| unremarkable [6,7].
|
| ...
|
| > Moreover, synergistic effects of TRL-Ab with exaggerated
| central nervous system (CNS) synthesis of human Ab are also
| suggested by the findings of accelerated amyloidosis in
| amyloid precursor protein/presenilin 1 (APP/PS1) mice
| maintained on atherogenic diets [9].
|
| Not saying keto is inherently an atherogenic diet, but
| surely saturated fat and salt isn't exactly avoided by most
| followers.
|
| > Just do a quick Google or YouTube search, lots of content
| on the subject.
|
| Yeah.......... sure. Content.
| notshift wrote:
| Mice trials don't interest me much. Human trials of
| various diets for Alzheimer's have been done along with
| lots of individuals who have tested it on themselves or
| family members with positive results.
|
| I can't find one of the more comprehensive studies I was
| looking at before, but a quick search pulls up this video
| which discusses a recent human trial which showed
| significant improvement on the keto diet (links to the
| study in description):
|
| https://youtu.be/jK6-r1zWOI0
| ketogenic wrote:
| Here is an example of a ketogenic diet: -
| 2 eggs - a cup of walnuts or almonds or pecans
| - eaten with a slice of cheese (4g saturated fat) -
| 3 tablespoons of chia seeds with water - peanuts
| and macadamia nuts as needed for hunger - steamed
| vegetables (broccoli, greens, Brussels sprouts, tomatoes)
| - eaten with 8 tablespoons of olive oil
| felixbraun wrote:
| avoid oxidized lipids and especially oxysterols
|
| very good primer:
| https://csroldsite.wordpress.com/2013/03/04/oxysterols-
| the-t...
| tux3 wrote:
| I'm curious how this squares up with the failure of drugs
| targeting beta-amyloid plaques. Despite some of these drugs
| being very effective at clearing Ab plaques, they don't seem to
| ever achieve any significant benefit in clinical trials.
|
| Reading Derek Lowe, you'd get the impression that the beta
| amyloid hypothesis is a formerly exciting thing of the past
| with a disastrous track record.
|
| >the relentless failure in this area, when amyloid plaques
| seemed for so long to be the most likely causative agent for
| the disease, is really something that makes you question
| things.
|
| >Add in the additional complete failures for every other
| attempt at the amyloid mechanism (secretase inhibitors, for
| example) and you start wondering if amyloid really is a cause
| of the disease or not
|
| Now Wikipedia is more optimistic:
|
| >The "amyloid hypothesis", that the plaques are responsible for
| the pathology of Alzheimer's disease, is accepted by the
| majority of researchers but is not conclusively established.
|
| I'm curious to see what comes out of this study, it's a very
| encouraging result. But it's hard to resolve this conflict of
| the mechanism looking great on paper, and completely failing in
| trials.
| goda90 wrote:
| Could it be that the amyloid-beta plaques are just a by-
| product of the same thing that is causing the damage in the
| first place?
| monopoledance wrote:
| From what I got from skipping over the study, this isn't
| about beta-amyloid itself, but "triglyceride-rich
| lipoprotein" amyloid beta _complexes_.
|
| The amyloid beta plaques may be not cause, but symptom of the
| disease. Maybe the TRL-A-betas are causing the damage, get
| metabolized and after that the protein separates and then
| accumulates in the brain? The study states, the TRL-A-beta
| are causing inflammation, which they attribute for disease
| progression rather than A-beta plaque formation.
|
| > ...the findings presented in this study nonetheless support
| a now large body of evidence that demonstrates that the
| genesis of plaque is not the initiating trigger for
| neurodegenerative processes to be initiated, but rather, may
| be consequential. This study provides evidence that more
| subtle chronic interactive effects of peripheral metabolism
| of TRL-Ab with the cerebrovasculature may be sufficient to
| potentially cause AD.
|
| So, clearing up A-betas may be just flushing the "damage
| logs".
| eightysixfour wrote:
| I only have a passing understanding, so forgive me if I get
| some of this wrong, but my understanding is that the beta
| amyloid hypothesis is "disproven" from the perspective that
| removing beta amyloid that has built up doesn't seem to
| resolve the symptoms. That is different than it isn't a
| causal link in the chain though.
|
| For example (making this up) I don't think we have disproven
| that beta amlyoid build-up causes inflammation, which
| actually causes the brain damage via a process that continues
| even once the beta amyloid is gone.
| tux3 wrote:
| What I find puzzling if the plaques are a link in the chain
| (as opposed to a symptom), isn't so much that beta-amyloid
| drugs stop short of outright resolving the symptoms, but
| that they don't seem to affect the progress of the disease.
|
| To continue with your example, if beta-amyloid was a major
| source of inflammation, and inflammation caused the damage,
| it'd seem reasonable to expect that removing the plaques
| would result in slowed cognitive decline.
|
| Strangely, this does not seem to happen in clinical trials.
| randcraw wrote:
| As I recall, several studies have also shown that people
| can have high levels of amyloid-beta plaques (ABPs) in the
| brain and not show any signs of dementia.
|
| Between the two outcomes (ABPs exist but there's no
| decline, and ABPs are removed but dementia persists), the
| prevailing interpretation is that ABPs _alone_ do not cause
| Alzheimer 's. They seem to arise along with the cognitive
| loss, though not cause it.
|
| Tau deposits and associated neurofibrillary tangles have
| also been implicated in dementia, but also can be absent in
| those with the disease, so they too are not directly
| causal.
| ortusdux wrote:
| How do these findings line up with the controversy surrounding
| Aducanumab?
| pedalpete wrote:
| Thanks for re-posting, I'm not sure how I missed this research,
| and even in Australia as well (I'm Sydney based).
|
| We're in sleep tech, building closed-loop SWO which of course
| has an impact on removal of beta-amyloids, but all the research
| I've seen to date has just not gone further than saying there
| is a "correlation" between Ass and Alzheimers.
|
| I'm not sure this completely closes the loop on cause-effect,
| but it seems a very strong bit of evidence. Not sure how I
| missed it before, but thanks.
| vimy wrote:
| Alzheimer isn't a disease but a symptom of chronic viruses and
| bacteria. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066504/
|
| People with Alzheimer have been cured after taking antibiotics.
| DantesKite wrote:
| I've heard similar evidence for Alzheimer's being essentially
| type III diabetes.
|
| I'm starting to think the causes can be multi-variate.
| mrtesthah wrote:
| > Using mouse models, researchers in Australia have identified
| one of the likely causes of Alzheimer's disease. Some have dubbed
| the finding a "breakthrough."
|
| Mice don't get alzheimer's.
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