quadhome
Alzheimer's is driven by the buildup of toxic proteins
called amyloid-beta.In the words of Derek
Lowe:Amyloid-directed therapies truly, truly do not appear
to be the answer for Alzheimer's treatment. When I started
work in the field back in the early 1990s, I was convinced
of the opposite - the evidence looked very strong that
defects in amyloid processing were indeed the cause of the
disease. But that was thirty-five years ago, thirty-five
years in which therapy after therapy after therapy aimed
at amyloid mechanisms has failed.[...] We're way past
persistence, way past focus, way past optimism and
multiple shots on goal and old-college-tries. Do something
else! For God's sake, do something else.-
https://www.science.org/content/blog-post/anti-amyloid-ant
ib...
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> cassepipe
This is just one person's (informed I assume) opinion
tough. It does sound like common sense but alas common
sense is rarely a good guide when it comes down to how
the body works.I don't have a dog in this fight and I
don't remember that much but I read someone's "in
defense of the amyloid hypothesis" with interest. So
if you want an counterpoint, you can go read
https://www.astralcodexten.com/p/in-defense-of-the-amy
loid-h...
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> > fnordpiglet
No actually there's a large body of quashed
research over these decades that went against the
prevailing hypothesis. It's one of the key
examples of how peer review fails to consider
novel approaches in the face of consensus even if
consensus is shown to likely be wrong. The fact
the original research driving the consensus was
fraudulent at worst made it that much more sad.To
be clear this isn't about whether it's right or
wrong it's about that science involves
investigating all avenues with evidence, proof,
and rigor. Group think is how we end up
incorporating bias into science, which is anti
scientific.
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> > > cassepipe
I believe you don't have read the link I
posted because its author does address the
narrative you present hereBut again I am not
saying you are wrong and I am even sympathetic
to this narrative but ultimately, unconvinced,
either way
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> dbcurtis
> Alzheimer's is driven by the buildup of toxic
proteins called amyloid-beta.Isn't the current
thinking that amyloid-beta buildup is a marker, not a
cause? The therapy may be working here, but it isn't
clear whether clearing amyloid-beta proteins is the
mechanism or an outcome.
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> > chermi
Yes. And to anyone paying attention, this has been
current since about 2010.
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> bluGill
I care what works, not about debate. This seems to
work and that trumps any debate about what the real
means are.Don't get me wrong, if you are in this area
of research this debate is important. There may be
other types of Alzheimer's that have a different
means. This drug may actually target something else.
There might be some other truth I haven't thought it -
but to me as an outsider the important part is a
treatment that works, not why it works.
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> > TaupeRanger
You are wrong. This paper very clearly does not
show that it "works". The debate exists for a good
reason - the very thing this paper claims to show
is the exact thing the person you replied to was
questioning. And that is a central question in all
of Alzheimer's research.There are dozens of
studies that show mice improving their
memory/spatial reasoning as Alzheimer's models.
None of them have led to a proven improvement in
longevity or quality of life for human Alzheimer's
patients. Some of them slightly slow the
progression, but even then you're getting into a
gray area - is it really "better" to be stuck in
the Alzheimer's fog for longer? Are we actually
improving quality of life? It's unclear.So no, in
order for us to say that this approach "works", we
would need randomized controlled clinical trials
in humans showing a strict improvement in quality
of life and/or longevity. This is not even close
to that level of evidence.
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> > vlovich123
I don't think anyone is against a treatment that
works, regardless of the mechanism.The problem is
that claimed success in these rat models has never
transferred to humans. Either the problem is that
rat Alzheimer's is a poor model for human
Alzheimer's or the science being done is poor
quality.> Because reducing amyloid burden is
clinically proven to improve functional outcomes,
these preclinical results strongly support the
rationale for testing this drug in early
symptomatic Alzheimer's diseaseI believe this is
the critical criticism of others. There's now two
camps. One side claims that the Amyloid movement
is based on faulty science and outright fraud
(true AFAIK) and the other side claims that
there's still evidence the amyloid hypothesis is
accurate despite the flawed start to the
hypothesis (possibly true). Generally I don't
trust a lot of effort being pushed behind a
hypothesis that's got such shady behavior from
proponents and that rely on fast tracking drug
approvals for drugs that reduce amyloids but
clearly don't benefit Alzheimer's. Everyone gets
to choose the priors they choose to evaluate the
situation on.
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> > > projektfu
If a beta-amyloid therapy eventually makes it
to successful trials, there will still be
people who believe the argument is already
over and the therapy cannot work. The problem
identified by Lowe and others is that some
amyloid-oriented researchers were not only
falsifying data but also acting as reviewers
and editors of journals and tanking
alternative explanations.That has stopped,
presumably, but alternative approaches haven't
had much success yet either.
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> > > > amluto
Therapies targeting amyloid deposits has
been tested extensively in actual humans,
and it indeed removes amyloid deposits.
The main problem is that none of the
therapies in question usefully treat
Alzheimer's disease.Sure, maybe an
eventual useful Alzheimer's therapy will
remove amyloid deposits, and maybe it
won't, but it needs to actually treat or
at least meaningfully slow the actual
disease.
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> > aBioGuy
In the title "....in the APP/PS1 Mouse Model of
Alzheimer's Disease"Given the decades of emphasis
on clearing / preventing amyloids I would be
fairly jaded. If someone (biotech) wants to spend
$$$ chasing this down, good on them.But a paper
curing a mouse model of a human neurological
disease does not move the needle for someone with
or watching someone suffer from this disease.
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> gwbas1c
The podcast "Why Has There Been So Little Progress on
Alzheimer's Disease?"
https://freakonomics.com/podcast/why-has-there-been-so
-littl... discusses a lot of the academic fraud that
lead to people following the Amyloid hypothesis.The
TLDR is that the researchers were publishing doctored
images to support their hypothesises, which is why the
Amyloid hypothesis was such a dead end.
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ebolyen
I think people are reacting to the press-release more than
the work.I don't see why this is definitely doomed just
because they discuss beta-amyloid plaques. Those exist and
are real. They probably don't cause it any more than
tombstones cause graveyards; very related, but not in the
directly mechanistic way we wish.> Alzheimer's disease
(AD) is a prevalent neurodegenerative disorder
characterized by the accumulation of amyloid-beta (Aβ)
peptides in the brain.This can be true and still not be
the specific mechanism.You can treat a specific waste
product or you can repair the waste stream. The issue may
be waste, but not a specific product, or the issue may not
be the waste stream at all.This work appears to
demonstrate evidence of waste stream repair via a
well-known waste-product. That doesn't mean that any
specific waste product is or is not the problem or that
this particular stream is definitely going to remove
enough of the waste (if that was the problem).Maybe there
have been a lot of drugs which have similarly attempted
waste-stream repair so there's good reason to doubt it on
that alone. But I don't think that mentioning beta-amyloid
plaque is enough to discard this out-of-hand.
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discretion22
Great news! If you are a mouse.For humans, not yet
progressed to trials though safety has been evaluated for
other diseases, so possible for trials to happen quickly?"
the compound has strong potential to quickly transition
into human clinics because it has already undergone safety
evaluations for other diseases."
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> onraglanroad
The Hitchhiker's Guide was right. We spend all our
time inventing new cures for the mice!
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> smallerize
A genetically modified mouse with human amyloid-beta
peptides. https://www.jax.org/strain/004462#
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> functionmouse
mice are having a great year
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djray
This pertinent paper appeared more than a decade ago about
the flaws in the amyloid plaque hypothesis:
https://pmc.ncbi.nlm.nih.gov/articles/PMC4207354/Many
people without dementia show amyloid plaques in their
brains in autopsies. It's becoming more accepted now that
there are multiple interrelated causes after decades
pursuing the simplistic amyloid plaque theory.The article
is bordering on irresponsible.
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avgDev
My mother has early onset alzheimer's disease. We
currently know very little about the disease and the
current treatment options are controversial. The efficacy
of the medications removing the amyloid plaque from the
brain is questionable, as people still decline.What makes
alzheimer's difficult is that it is not really a single
uniform disease. There are subtypes.Since my mother has
it, I was presented with an option of a genetic test.
There are several genes which increase your risk. However,
if one has PSEN1 that will 100% guarantee early onset
alzheimer's at some point.I'm still on the fence if I want
to know.I really hope we get some viable treatments for
this terrible disease. Early onset azlheimer's is awful. I
cannot imagine having malfunctioning brain.
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adamredwoods
Lithium, too! In mice.
https://otd.harvard.edu/news/could-lithium-explain-and-tre
at...
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> helterskelter
Interestingly, lithium does seem to protect telomeres
and in fact lengthens them, which may affect
Alzheimer's.
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IAmBroom
"Alzheimer's is driven by the buildup of toxic proteins
called amyloid-beta."That's the predominant theory, but
nothing affecting them has yet proven to be efficacious so
far (AFAIK).Likewise, at one time everyone "knew" aluminum
was a culprit, because it showed up in autopsy analyses of
affected people. However, it turned out that correlation
wasn't from aluminum causing it, so avoiding aluminum
didn't affect the disease.
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ck2
btw definitely related and seems significant:they found
people who use glucosamine (joint pain, knees etc)have a
25% higher chance of Alzheimer's
progressionhttps://thesciverse.org/scientists-found-that-a
-supplement-t...(still can't figure out if that website is
"AI" but they have great articles)
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> plaguuuuuu
Yep it's all AI-generated. It's annoying that they
have a fake human as the author but whatever, it's the
interslop.
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TaupeRanger
Flagged. Nonsense puff piece by the university. The
headline itself is beyond terrible - this is a mouse model
and would need years of further successful research to be
able to say that it "restores memory" in any meaningful
way, let alone in actual humans.
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> Selkirk
The linked article is intentionally misleading by
omission because they left out "in mice" in the
university driven article and they certainly know the
relevance and consequences of leaving it out.
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> musiciangames
Yes, it's really disappointing to see Monash doing
that - not a mention of mouse or mice.
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> > contingencies
AFAIK the background is the 'big 5' universities
in Australia have a fat loan due which they took
out 10 years ago and can't pay. Their primary
income source was foreign exchange students and
that demand has fallen off a cliff. So they're
shedding academics and puffing like crazy right
now. It seems in the near future Australian
tertiary education will be highly corporatized and
move to a more American model than our
European-style history.
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