Scientists say they might have discovered the cause of Alzheimer's

[malaise]

https://www.newsbreak.com/news/2449842341506/scientists-say-they-might-have-discovered-the-cause-of-alzheimer-s?noAds=1&_f=app_share&s=i0

Researchers at the University of California-Riverside published results of a study that analyzed donated brain samples.
They focused on the form of tau proteins, which are important amino acids that can be either right-handed or left-handed.
Researchers discovered that those who had a “different handed” form of tau proteins along with brain plaque and tangles also had dementia.
Scientists in California tried to study Alzheimer’s disease from a different perspective and the results may have led them to the cause of the disease.

[Lucid Dreamer]

1. Thank you so much for this.

Very interesting. I hope there is breakthru progress coming soon.

[malaise]

2. You're welcome

[cilla4progress]

3. I'm not understanding.

Being left-handed, am I more prone?

[malaise]

4. I didn't get that impression but I'll let the DU medics and scientists weigh in

This is way above my pay grade

[cilla4progress]

5. Thanks!

[panader0]

9. I don't think those terms are about actual left or right handedness.

I think it's about the brain. I'll learn more about this if I can remember.

[Rebl2]

42. No I

Don’t think so either.

[Klaralven]

11. No. It refers to the "handedness" of the chemical molecules

A chiral molecule or ion exists in two stereoisomers that are mirror images of each other, called enantiomers; they are often distinguished as either "right-handed" or "left-handed" by their absolute configuration or some other criterion. The two enantiomers have the same chemical properties, except when reacting with other chiral compounds. They also have the same physical properties, except that they often have opposite optical activities. A homogeneous mixture of the two enantiomers in equal parts is said to be racemic, and it usually differs chemically and physically from the pure enantiomers.

https://en.wikipedia.org/wiki/Chirality_(chemistry)

[Bernardo de La Paz]

30. I wonder if artificial sweeteners may play a role in Alzheimer's

From your link ( Chirality (chemistry) )

Manifestations of chirality

Flavour: the artificial sweetener aspartame has two enantiomers. L-aspartame tastes sweet whereas D-aspartame is tasteless.[7]
Odor: R-(–)-carvone smells like spearmint whereas S-(+)-carvone smells like caraway.[8]
Drug effectiveness: the antidepressant drug Citalopram is sold as a racemic mixture. However, studies have shown that only the (S)-(+) enantiomer is responsible for the drug's beneficial effects.[9][10]
Drug safety: D‑penicillamine is used in chelation therapy and for the treatment of rheumatoid arthritis whereas L‑penicillamine is toxic as it inhibits the action of pyridoxine, an essential B vitamin.[11]

[Klaralven]

37. Unlikely, most compounds used in living organisms have handedness

Must the Molecules of Life Always be Left-Handed or Right-Handed?

One of the strangest aspects of life on Earth—and possibly of life elsewhere in the cosmos—is a feature that puzzles chemists, biologists and theoretical physicists alike. Each of life’s molecular building blocks (amino acids and sugars) has a twin—not an identical one, but a mirror image. Just like your right hand mirrors your left but will never fit comfortably into a left-handed glove, amino acids and sugars come in both right and left versions. This phenomenon of biological shape selection is called “chirality”—from the Greek for handedness.

On Earth, the amino acids characteristic of life are all “left-handed” in shape, and cannot be exchanged for their right-handed doppelgänger. Meanwhile, all sugars characteristic of life on Earth are “right-handed.” The opposite hands for both amino acids and sugars exist in the universe, but they just aren’t utilized by any known biological life form. (Some bacteria can actually convert right-handed amino acids into the left-handed version, but they can’t use the right-handed ones as is.) In other words, both sugars and amino acids on Earth are homochiral: one-handed.

https://www.smithsonianmag.com/space/must-all-molecules-life-be-left-handed-or-right-handed-180959956/

The new Alzheimer discovery may be an interesting exception to the general thesis of the Smithsonian article.

[Bernardo de La Paz]

47. Summary: for life amino acids are lefties & sugars righties. But L-aspartame is left.

It is the way that it seems to go against the pattern that stands out for me.

However, aspartame is not a sugar. It's an ester of two amino acids. On the face of it, that would not seem to be a problem since leftie amino acids are useful to organisms.

There seems to be some evidence of a linkage but not definitive.

https://www.theadvocate.com/baton_rouge/entertainment_life/health_fitness/article_a90e1b7c-76d9-11eb-b1d2-97418f7a49d8.html

I avoid all artificial sweeteners including sucralose.

[GB_RN]

77. Only In That They Might Increase The Likelihood Of Getting It...

But there's also genetic component to Alzheimer's that can make you can be more likely to acquire the disease, in addition to the rare, but inheritable 1-2% of cases that cause early onset Alzheimers. It's a definitely a complicated and multifactorial disease process.

But with respect to the chemistry you referenced, the disease was first diagnosed over 100 years ago (by German psychiatrist Alois Alzheimer in 1906), well before any of those compounds were discovered.

We covered all that in nursing school, which is how I know about it (even if it's not my area of expertise: I'm a cardiac cath lab RN).

[malaise]

58. Thanks for this

[malthaussen]

12. Nope, nothing to do with it.

"Handnessness" in proteins refers to the way they are structured on a molecular level. Nothing at all to do with which hand you use.

-- Mal

[diverdownjt]

16. A molecule can be left handed or right handed...

depends on the direction the particles are arranged in...right spiral or left, also known as chirality. It changes how molecules can interact with one another. Spiral may not be correct but this is what I remember from college chem class. Two molecules can be
identical in every way but reverse chirality.

[JohnSJ]

18. I believe they are referring to mirror images, enantiomers of a chemical, in this case the protein

they are examining

These compounds have identical chemical properties except for their ability to rotate polarized amounts by equal amounts, but opposite direction, clockwise or counterclockwise, left or right.

[cos dem]

23. Think of a corkscrew

It could be right-handed (turn clockwise) or left-handed (turn counterclockwise). They’re both corkscrews, but structurally are mirror images.

Many complex molecules look like complicated corkscrews.

[olegramps]

33. I believe they are referring to the molecular orientation protein. It is like mirror image.

[Silent3]

64. This is about a chemical property called "chirality"

Two molecules can be identical to one another in chemical composition, but each with a structure that is a mirror image of the other. This often makes a big difference in biochemistry in how a substance behaves.

[colsohlibgal]

6. Interesting

I am 100% ambidextrous wonder how that works with people like me?

[NCjack]

53. The molecular property being discussed doesn't relate to your hands. Instead, it is a 3D property

of tau protein molecules that have the same elemental composition and 3D structures that are mirror images.

Moving away from "hands", assume that in a accident, your left ear was destroyed. In a search for a replacement ear, you find only a "right" ear. It will not work. And, "left-ear" tau proteins are not interchangeable with "right-ear" tau proteins in the chemistry of the brain.

[panader0]

7. Hurry up, I'm getting old.

My dad had dementia--it was bad--my mom had died and my twins were small babies.
I needed to take care of him, shopping and cleaning his house. Then my older brother got
early onset dementia and the VA hospitalized him. He passed in June.
I'm hoping I take after my mom's side of the family where everyone was sharp until they died.
If I sense dementia coming on, I'll end myself, it's too much of a burden to lay on others.
I may try LSD again, it could break up that brain plaque.
https://mind-foundation.org/psychedelics-alzheimers-disease-treatment/

[malaise]

10. My father's youngest sister had it

She was almost 97 when she died and had it for the last three to four years - she didn't recognize anyone by then.

[OhZone]

17. So they buried the headline in the OP - the cure is a little more autophagy!

https://www.medicinenet.com/how_do_you_trigger_autophagy/article.htm

[cilla4progress]

26. Yes,

my husband I do intermittent fasting most days. Triggers autophagy!

[lindysalsagal]

35. Exercise is also listed as preventative. I swear by my daily treadmill. No muscle strain

but sustainable cardio and muscle work. Plus, I listen to things like music or language audio books, so, I get a mental workout, as well. Then I do some light weights, again, sustainable daily. Not heavy, just regular.

[malaise]

59. I walk 5.2K four days a week and ride the stationary bike the other three days.

I exercise for an hour after walking or riding.
Do puzzles and watch quiz shows daily as well.

[malaise]

60. I walk 5.2K four days a week and ride the stationary bike the other three days.

I exercise for an hour after walking or riding.
Do puzzles and watch quiz shows daily as well.

[shanti]

69. Well

Mother used to go to the gym every day....until she developed dementia. She did live to 88, longer than her siblings and parents. But I do understand exercise helps as far as strengthening muscles to support weaker bones, helps with balance, etc.

[Laura PourMeADrink]

43. Thank you - very interesting article. Did take pause with this typo tho

Curcumin:
Curcumin is a naturally occurring chemical found in the popular spice, turmeric. Some animal studies suggest that its intake might trigger autopsy

[OhZone]

48. LOL

That's a pretty bad typo!

[KS Toronado]

8. Hate it when my left hand doesn't know what my right hand is doing

something was begging me to say that, LOL

[diverdownjt]

20. And you having nooo impulse control(like me) just had to say it.

[cilla4progress]

13. Ahh....

thanks.

Well INTERMITTENT FASTING which my husband and I do more or less regularly, seems to help prevent or slow it!

I started doing it for high blood glucose. It brought it down!

We eat in about an 8 hour window - noon to 8. That's it (or at least we try most days). I highly recommend it! There's lots of info online about it.

[AnotherDreamWeaver]

72. Do you eat one meal between noon and 8?

Or do you snack between those hours, or have lunch and a dinner?

[bucolic_frolic]

14. Good, now could they please turn their attention to the cause of stupidity?

[pandr32]

15. I hope this will save people soon

The 'golden years' should not be spent with dementia. Too many care facilities that house demented older adults are deplorable. I visited one with my sister (our mother had dementia) to see several resident patients strapped in wheelchairs and left in hallways for long stretches of time with no windows--no stimulation at all. This was supposed to be topnotch, too. We said "no way!".

[Laura PourMeADrink]

46. That is so true about nursing homes. It's a travesty

the way people are treated even those without dementia. And then because they weren't equipped and because FG didn't warn them, so many people died of covid.

But you know, I don't think people even realize until you have to go through it with your parents. You have to be wealthy to afford decent residential eldercare. Or divest any assets accumulated over the years as meager as they may be. Definitely something to the old custom of taking in your elders to live with you for as long as you can.

[pandr32]

65. The care facility we looked at for Mom was upscale.

I can't imagine how horrible ones in poorer areas are. We need to value our elders more and quit using them for massive profit.

[OhZone]

21. The issue is reduced autophagy in older folk, huh?

Oh - oh - oh! Maybe that's why turmeric is so helpful! And other things!

https://www.medicinenet.com/how_do_you_trigger_autophagy/article.htm

[cilla4progress]

34. Haha - was just going to post

identical article!

Well worth a read.

Turmeric, exercise, intermittent fasting, good night's sleep, high fat/low carb diet.

[AnotherDreamWeaver]

73. OK, I read the post above from OhZone.

It answered my questions. Thanks

[question everything]

22. A welcomed news. Tau has been studies before so I hope that these studies

will continue.

Certainly more promising than the amyloid plaques which, after wasted resources have led to nothing. Many have amyloid plaques with no sign of dementia.

[Bernardo de La Paz]

24. The Tau hypothesis has been around since at least 2009

I'm not sure how this is news.

https://en.wikipedia.org/wiki/Tau_protein#Tau_hypothesis_of_Alzheimer's_disease

[Act_of_Reparation]

28. The mechanics of the tau hypothesis are still being studied.

And when one discovers something about said mechanics, it gets filed under "news".

[Bernardo de La Paz]

29. Okay, thank you. . . . nt

[Act_of_Reparation]

25. Chirality.

Makes sense.

[hibbing]

27. Took my mom, hope there is a treatment/prevention soon n/t

[OhZone]

31. So looks like this is whatcha got to do to help prevent Alzheimers -

Factors that trigger autophagy:

Intermittent fasting!

Eat a high-fat, low-carb diet!

Exercise!

Good sleep!

Curcumin!


https://www.medicinenet.com/how_do_you_trigger_autophagy/article.htm

[Wingus Dingus]

32. So would the constant ingestion of proteins lead to a decrease

Last edited Thu Dec 2, 2021, 03:09 PM - Edit history (1)

in the beneficial process of autophagy, leading to Alzheimers in susceptible people? My understanding of these findings is that when the brain is temporarily deprived of proteins (via fasting), the brain cells scavenge excess proteins already present, which prevents this defective tau protein from building up too much. I wonder how high protein diets (which seem to be everywhere now, as a part of the low carb trend) contribute to dementia? Hope they figure it out soon, because the US doesn't fast or exercise and we eat a ton of protein as a culture.

[OhZone]

36. Well, low carb can be -

high fat and low carb, not high protein, low carb.

I guess.

So eat a little less protein with your low carb and more Smart balance? ha

[Wingus Dingus]

40. My family is chock full of: Alzheimers, heart disease, and diabetes.

I was trying to get more protein and less carbs in my diet, but now I guess I'll try to just do an everything-in-moderation plus fasting/exercise approach until more info comes out. (I can't do high-fat, my guts can't take it, lol.)

[mainer]

38. Similar to prion- related Creutzfeldt-Jakob .

That’s also related to protein misfolding

[OhZone]

41. What happened to that guy who said -

Mad cow was from the insecticide and it's effects on copper/magnesium balance - making the prions fold - not a communicable disease?

He said his organic cows didn't get it but the one's treated forwarble fly did.

[hamsterjill]

39. I hope this is true.

We could all use some good news, couldn't we? Every step forward in this research is one step closer to understanding and finding a cure. So I applaud the efforts.

[talking-liberally]

44. Meat and dairy are the primary causes of dementia

https://nutritionfacts.org/video/how-to-prevent-alzheimers-with-diet/

[OhZone]

50. Well I guess that could mirror the idea that it's too much protein not being cleared out!

[talking-liberally]

55. Good point.

We put way too much emphasis on protein. 97% of Americans get the recommended protein but the majority don't get even half the recommended amount of fiber. We don't have a protein problem, we have a fiber problem.

[malaise]

61. Interesting

I haven't eaten red meat since 1979, but I do eat seafood and bird.
I never liked mil and hate all cereal outside of granola and oatmeal cookies. I do like ice cream now and then. And cheese and butter are quite popular here.

[relayerbob]

45. Thanks for info and link

My father had it, so I have my concerns also, and at 64, ain't gettin' any younger!

[Sogo]

49. A good dose of Ivermectin will take care of it.

(just in case anyone didn't get it....)

[OhZone]

51. HA -

I wouldn't be surprised if ivermectin could cause it really.

[malaise]

76. ROFL

[NNadir]

52. That is not a cause. It's just another biomarker. N/t

[MontanaMama]

54. I lost my dad and granddad to early onset Alzheimer's.

It is my fervent hope that researchers find the cause and can treat it. I worry that I'm next.

[mahina]

56. Has anyone been able to read through the link?

I can’t find any of the researchers to het to an abstract of the study. The article summary says it was published so I searched terms “pubmed” “tau proteins” “dementia” “autophagy” and again with those and “different handed”

The different handed bit was not found but several other studies dating back years included the other terms. It would be terrific to include the authors.

In case anyone didn’t know, search term “pubmed” with any medical question yields peer reviewed journal articles with citations and at least summaries.

Mahalo Malaise. We keep hope.
https://pubmed.ncbi.nlm.nih.gov/29024336/
Interplay of pathogenic forms of human tau with different autophagic pathways
Benjamin Caballero et al. Aging Cell. 2018 Feb.
Free PMC article
Show details

Full text links
Cite

Abstract

Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies. Aberrant turnover of tau, a microtubule-stabilizing protein, contributes to its accumulation and subsequent toxicity in tauopathy patients' brains. A direct toxic effect of pathogenic forms of tau on the proteolytic systems that normally contribute to their turnover has been proposed. In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this age-related disease. We have found that the pathogenic P301L mutation inhibits degradation of tau by any of the three autophagic pathways, whereas the risk-associated tau mutation A152T reroutes tau for degradation through a different autophagy pathway. We also found defective autophagic degradation of tau when using mutations that mimic common posttranslational modifications in tau or known to promote its aggregation. Interestingly, although most mutations markedly reduced degradation of tau through autophagy, the step of this process preferentially affected varies depending on the type of tau mutation. Overall, our studies unveil a complex interplay between the multiple modifications of tau and selective forms of autophagy that may determine its physiological degradation and its faulty clearance in the disease context.

Keywords: Alzheimer's disease; aging; autophagy; frontotemporal dementia; lysosomes; neurodegeneration.

© 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

[malaise]

63. Hi there

I haven't linked the original article either

[mahina]

68. Raja

🤙🏼🤙🏼✨🌸

[SunImp]

57. I hope they find a cure within my lifetime

[malaise]

62. That's what I told the sis who sent this

It would save both lives and a lot of pain for families of patients with this horrific disease.

[Red Pest]

66. Did any one actually read the paper or at least the abstract?

Title: Does Data-Independent Acquisition Data Contain Hidden Gems? A Case Study Related to Alzheimer’s Disease

Abstract: One of the potential benefits of using data-independent acquisition (DIA) proteomics protocols is that information not originally targeted by the study may be present and discovered by subsequent analysis. Herein, we reanalyzed DIA data originally recorded for global proteomic analysis to look for isomerized peptides, which occur as a result of spontaneous chemical modifications to long-lived proteins. Examination of a large set of human brain samples revealed a striking relationship between Alzheimer’s disease (AD) status and isomerization of aspartic acid in a peptide from tau. Relative to controls, a surprising increase in isomer abundance was found in both autosomal dominant and sporadic AD samples. To explore potential mechanisms that might account for these observations, quantitative analysis of proteins related to isomerization repair and autophagy was performed. Differences consistent with reduced autophagic flux in AD-related samples relative to controls were found for numerous proteins, including most notably p62, a recognized indicator of autophagic inhibition. These results suggest, but do not conclusively demonstrate, that lower autophagic flux may be strongly associated with loss of function in AD brains. This study illustrates that DIA data may contain unforeseen results of interest and may be particularly useful for pilot studies investigating new research directions. In this case, a promising target for future investigations into the therapy and prevention of AD has been identified.

Note that this study only suggests that isomerization by an amino acid racemase may/might contribute to the tau tangles causing Alzheimer's disease. Clearly this study needs to be repeated and extended - as the authors indicate in the last sentence of the abstract. While neuroscience is not my field of study (I am a microbiologist), I have read several papers claiming that various molecules or the lack of certain activities or whatever is the cause of AD. Thus, like in all scientific discovery, we need to see the result repeated and extended. This group of scientists have made an observation which allows them to propose a hypothesis. That hypothesis will be tested and, depending upon the results, will be modified or discarded. Eventually, it may rise to the level of theory (aka demonstrated as correct). Stay tuned, maybe in a year or two you will see some follow-up that confirms or rejects this set of observations.

[malaise]

67. The Headline says MIGHT

as does the abstract

[spanone]

71. ...K&R...

[JT45242]

74. Correlation not necessarily causality

The correlation between the two may be that the effect of Alzheimer's is the wrong chirality (handedness) of these proteins.

One of the BIG PROBLEMS in doing alzheimer's or any other human medical research is that you are looking backward at correlations and can rarely do experiments that test causality. Now, if they were to somehow do a study and found the wrong chirality proteins in people who LATER developed Alzheimer's it would potentially satisfy part of the causality rule for science.

Causality requires correlation and antecedence (the cause MUST occur before the effect). There was a great book on how bad people are at judging causality and their confirmation by a group under Deanna Kuhn back in the 1980s.

Until then, all we can say is that this study found a correlation between the two which may imply chirality causes Alzheimer's, Alzheimer's causes faulty chirality, or some other factor or factors causes both. For now, all three possibilities are possible.

However, claiming you found a possible cause in press releases is a great way to get increased funding to your research on what to many of us is a terrifying disease.

[ShazzieB]

75. I'm convinced that most people don't really understand

the difference between correlation and causality. Or at least they're way too quick to mistake the former for the latter. It's such a common area of confusion that I can't help but think this probably needs to be more heavily emphasized in basic science classes.

Confusing the two is the source of SO many problems, including vaccine hesitancy (in general, not covid specifically). As in "My kid was diagnosed with autism after receiving vaccines, so vaccines obviously cause autism hurr durr!"

[lark]

79. Wow, I read about fasting being helpful to the brain from a nutrition book, but amazing to see this.

Can't wait for more information about what length of fasting is recommended. I am going to talk to my husband about no snacking after 8, I am already doing this for the most part.