Alzheimer's symptoms could be due to decline in brain protein not accumulation of amyloid plaques:
Experts estimate more than 6 million Americans are living with Alzheimer's dementia. But a recent study, led by the University of Cincinnati, sheds new light on the disease and a highly debated new drug therapy.
The UC-led study, conducted in collaboration with the Karolinska Institute in Sweden, claims that the treatment of Alzheimer's disease might lie in normalizing the levels of a specific brain protein called amyloid-beta peptide. This protein is needed in its original, soluble form to keep the brain healthy, but sometimes it hardens into "brain stones" or clumps, called amyloid plaques.
[...] "It's not the plaques that are causing impaired cognition,'' says Alberto Espay, the new study's senior author and professor of neurology at UC. "Amyloid plaques are a consequence, not a cause," of Alzheimer's disease, says Espay, who is also a member of the UC Gardner Neuroscience Institute.
[...] Cognitive impairment could be due to a decline in soluble amyloid-beta peptide instead of the corresponding accumulation of amyloid plaques. To test their hypothesis, they analyzed the brain scans and spinal fluid from 600 individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative study, who all had amyloid plaques. From there, they compared the amount of plaques and levels of the peptide in the individuals with normal cognition to those with cognitive impairment. They found that, regardless of the amount of plaques in the brain, the individuals with high levels of the peptide were cognitively normal.
They also found that higher levels of soluble amyloid-beta peptide were associated with a larger hippocampus, the area of the brain most important for memory.
According to the authors, as we age most people develop amyloid plagues, but few people develop dementia. In fact, by the age of 85, 60% of people will have these plagues, but only 10% develop dementia, they say.
Journal Reference:
Andrea Sturchio. High cerebrospinal amyloid-β 42 is associated with normal cognition in individuals with brain amyloidosis, EClinicalMedicine (DOI: 10.1016/j.eclinm.2021.100988)
(Score: 4, Funny) by KilroySmith on Wednesday July 14 2021, @08:18PM (4 children)
I love the way the article switches from "plaques" to "plagues".
I noticed "...60% of people will have these plagues" - I think that would qualify as an even more serious problem....
(Score: 4, Funny) by DannyB on Wednesday July 14 2021, @08:36PM (3 children)
I only count two plagues in TFA and in the portion quoted by upstart.
Two isn't so bad. It's not like the article's authors are getting dementia or something.
While Republicans can get over Trump's sexual assaults, affairs, and vulgarity; they cannot get over Obama being black.
(Score: 3, Funny) by sgleysti on Wednesday July 14 2021, @09:34PM (2 children)
Nor is it as though the article is plagued with spelling mistakes.
(Score: 2) by DannyB on Wednesday July 14 2021, @09:44PM (1 child)
That's not as bad as getting plaqued with spelling mistakes.
While Republicans can get over Trump's sexual assaults, affairs, and vulgarity; they cannot get over Obama being black.
(Score: 0) by Anonymous Coward on Wednesday July 14 2021, @10:29PM
Could've been infested with phages! You are so lucky! Back in the day, when I was young, we used to, . . . where was I going with this?
(Score: 4, Insightful) by Snotnose on Wednesday July 14 2021, @10:00PM (9 children)
So you mean the FDA's recent approval of a drug that doesn't work is solving a problem that isn't a problem?
/ clutches handbags, looks for smelling salts
// whatever is this world coming to?
/// well, guess it works for those folks on the receiving end of the 58k per year per patient
I just passed a drug test. My dealer has some explaining to do.
(Score: 2) by legont on Wednesday July 14 2021, @10:52PM (7 children)
The problem is the price of the drug which is $75000 per year if my Alzheimer serves me correctly. I am sure scientists of the world will fight this hard.
"Wealth is the relentless enemy of understanding" - John Kenneth Galbraith.
(Score: 4, Insightful) by sjames on Wednesday July 14 2021, @11:14PM (4 children)
The problem is twofold. First, it doesn't work. Second, it costs $75000/year. The old snake oil didn't work either, but at least it had alcohol in it and it was cheaper.
(Score: 5, Informative) by HiThere on Wednesday July 14 2021, @11:22PM (3 children)
There's a third problem. As well as not working, it also has frequent serious side effects.
https://www.dementiacarecentral.com/aboutdementia/treating/aducanumab [dementiacarecentral.com]
Javascript is what you use to allow unknown third parties to run software you have no idea about on your computer.
(Score: 1, Funny) by Anonymous Coward on Wednesday July 14 2021, @11:41PM (1 child)
Badakathcare!
(Score: 4, Insightful) by sjames on Thursday July 15 2021, @12:06AM
I love the way they downplay it by calling swelling and bleeding in the brain an "imaging abnormality" as if the problem is just a smudge on the lens or something.
(Score: 2) by JoeMerchant on Thursday July 15 2021, @12:05AM
Don't worry, I can fix that [youtube.com]!
Україна досі не є частиною Росії Слава Україні🌻 https://news.stanford.edu/2023/02/17/will-russia-ukraine-war-end
(Score: 0, Offtopic) by HammeredGlass on Wednesday July 14 2021, @11:48PM (1 child)
Why would scientists or doctors fight the high costs of healthcare they are responsible for? They have hundreds of thousands of dollars of medical school bills to pay off which were set by other doctors and scientists. And they all have Porsches and mansions to buy.
(Score: 0) by Anonymous Coward on Thursday July 15 2021, @04:31PM
Because they would make more money if the overall price comes down so more people can afford care? Most of the high cost of healthcare comes from the medical supply industry, including pharmaceutical companies, overcharging for their products.
(Score: 0) by Anonymous Coward on Thursday July 15 2021, @04:04AM
This is completely disingenuous. That drug works perfectly well in his primary function. It just happens that that primary function is to make big pharma massive amounts of profit.
In completely unrelated news, Moderna stock is up about 2000% since the start of this plague.
(Score: 0) by Anonymous Coward on Wednesday July 14 2021, @11:18PM (8 children)
"Damage to the cholinergic (acetylcholine-producing) system in the brain has been shown to be associated with the memory deficits associated with Alzheimer's disease.[13] ACh has also been shown to promote REM sleep."
https://en.wikipedia.org/wiki/Acetylcholine [wikipedia.org]
I'm too lazy to do any digging but I wonder if acetylcholine is a precursor to amyloid-beta peptide.
"β-Amyloid-acetylcholine molecular interaction: new role of cholinergic mediators in anti-Alzheimer therapy?
"Background: For long time Alzheimer's disease has been attributed to a cholinergic deficit. More recently, it has been considered dependent on the accumulation of the amyloid beta peptide (Aβ), which promotes neuronal loss and impairs neuronal function. Results/methodology: In the present study, using biophysical and biochemical experiments we tested the hypothesis that in addition to its role as a neurotransmitter, acetylcholine may exert its action as an anti-Alzheimer agent through a direct interaction with Aβ. Conclusion: Our data provide evidence that acetylcholine favors the soluble peptide conformation and exerts a neuroprotective effect against the neuroinflammatory and toxic effects of Aβ. The present paper paves the way toward the development of new polyfunctional anti-Alzheimer therapeutics capable of intervening on both the cholinergic transmission and the Aβ aggregation."
https://www.future-science.com/doi/10.4155/fmc-2016-0006 [future-science.com]
It seems the article is paywalled ...
(Score: 1) by HammeredGlass on Wednesday July 14 2021, @11:53PM (3 children)
They pair a lot of different anticholinergics with Schedule III-IV drugs to inhibit abuse, and which are naturally abused by the recreational and Rx crowds.
(Score: 2) by NickM on Thursday July 15 2021, @01:13AM (2 children)
Unless the anticholinergic is something brutal like atropine, it's hard to tell if the goal is deterrence or pharmaceutical synergy.
Take Tussionex [webmd.com], for example, the antihistamine is decently anticholinergics yet for the stated goal of masking flu/cold symptoms it's a good combination.
I a master of typographic, grammatical and miscellaneous errors !
(Score: 0) by Anonymous Coward on Thursday July 15 2021, @12:44PM
Yellow Tussionex has long been the preferred cough syrup for recreational use, and it fetches a hefty price - $50-100/oz is normal.
(Score: 1) by HammeredGlass on Thursday July 15 2021, @03:21PM
Meperidine has similar chemical structure to atropine.
(Score: 0) by Anonymous Coward on Thursday July 15 2021, @10:58AM (3 children)
(same poster)
"the treatment of Alzheimer's disease might lie in normalizing the levels of a specific brain protein called amyloid-beta peptide. This protein is needed in its original, soluble form to keep the brain healthy, but sometimes it hardens into "brain stones" or clumps, called amyloid plaques."
So I wonder if the trials intended to remove these plaques could actually make the dementia worse? Le Chatelier's Principle would say that if you remove products (the plaques) the reactants to those products (amyloid-beta peptide in its soluble form) will start to form products faster reducing the concentration of reactants (reducing the concentration of amyloid-beta peptide further). So by removing the plaques could you then be reducing the concentration of amyloid beta peptide?
It's possible that the solubility of amyloid-beta peptide somehow gets reduced. I wonder what amyloid-beta peptide is most soluble in that the brain usually has more of that it perhaps it has less of with people with Alzheimer's. There might be something that the brain produces that dissolves the peptide that gets produced in lesser quantities with Alzheimer's patients but the effects are not as noticeable at a younger age because you produce more (less than average but still more than what you would produce at an older age) but at an older age it becomes more noticeable.
(Score: 0) by Anonymous Coward on Thursday July 15 2021, @11:16AM (1 child)
(and, obviously, that's why I posted the article on acetylcholine)
"acetylcholine favors the soluble peptide"
(from the original comment)
(IOW, do people with Alzheimer's disease perhaps have less acetylcholine, especially at an old age, than people without and hence this results in less of the desired soluble form. I believe older people do have less acetylcholine and acetylcholine supplements have been supposedly shown to reduce the effects of Alzheimer's? I wonder if such supplements also correlate to fewer plaques and more of the soluble form of the peptide).
(Score: 0) by Anonymous Coward on Thursday July 15 2021, @09:02PM
Now that I think about it further non-Alzheimer's related dementia might simply be due to a lack of amyloid beta peptide (without the formation of amyloid beta plaques).
It could either be that amyloid beta peptide is not present in the first place for whatever reason (hence the plaques don't form since there are no 'reactants' so to speak or no starting material) or that the peptide is poorly soluble, forms plaques, but the brain or immune system keeps removing it before the plaques can build up hence it's not detectable.
In the case where amyloid beta peptide is simply absent acetylcholine might not help.
(Score: 0) by Anonymous Coward on Saturday July 17 2021, @10:43AM
(same poster)
Now I just remembered this study about sleep and the clearance of amyloid beta. Sufficient sleep has been shown to potentially reduce the chances of getting Alzheimer's and/or the severity of Alzheimer's. Sleep has been shown to clear out Amyloid Beta.
"They found that sleep changes the cellular structure of the brain and plays a critical role in beta-amyloid clearance. Their findings included:
Space between neurons increased 60% during sleep and anesthesia, resulting in an increased exchange
of CSF and interstitial fluid (Figure 2).
CSF influx into the interstitial space in awake mice was only about 5% of the CSF
influx in sleeping or anesthetized mice.
Sleeping and anesthetized mice cleared twice as much beta-amyloid from their brains as conscious mice"
https://www.alz.org/media/documents/inbrief-sleep.pdf [alz.org] [PDF file]
So are they talking about the clearance of dissolved Amyloid beta peptide or of amyloid beta plaques (I'm assuming the dissolved form)? Or am I just missing something?
(Score: 2, Interesting) by HammeredGlass on Wednesday July 14 2021, @11:41PM (1 child)
https://en.wikipedia.org/wiki/Long-term_effects_of_cannabis#Brain [wikipedia.org]
(Score: 2) by NickM on Thursday July 15 2021, @12:38AM
The study in the wikipedia ref is using some potentially funky statistical technique:
While there is that publication¹ [nih.gov] from a journal with a similar impact
factor as the reference on wikipedia :
1- Also using some potentially funky statistical technique !
2- The reported neurogenesis is in direct contraction with that wikipedia reference!
3- On real nonrodents humans !
In concussions I would like to add my voice to the researchers from the second article:
I a master of typographic, grammatical and miscellaneous errors !
(Score: 1, Insightful) by Anonymous Coward on Thursday July 15 2021, @03:05AM (1 child)
Get ready for the onslaught from the "supplements" industry. All they need is ONE article like this to kick off a whole new snake oil campaign. There's going to be a shitload of soluble amyloid-beta peptide enhanced products "clinically proven to prevent Alzheimer's*". There's going to be gummies with "the most soluble amyloid-beta peptides in the industry", soluble ABP breakfast cereals, toothpaste, etc.
* These statements have not been evaluated by the Food and Drug Administration and this product is not intended to prevent or cure any disease.
(Score: 0) by Anonymous Coward on Thursday July 15 2021, @06:20AM
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