
Tau PET imaging beats amyloid-based approach in battle against Alzheimer’s - howard941
https://www.healthimaging.com/topics/molecular-imaging/tau-pet-imaging-beats-amyloid-battle-alzheimers
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reasonattlm
A prediction: the generic, low-cost drug dasatinib, a senolytic that
selectively destroys senescent cells and can pass the blood-brain barrier,
will be the best Alzheimer's treatment of the next decade, starting just as
soon as the Mayo Clinic gets around to running a trial for that rather than
focusing on fibrotic disease.

[https://doi.org/10.1111/acel.12840](https://doi.org/10.1111/acel.12840)

"Tau transgenic mice with late stage pathology were treated with senolytics to
remove senescent cells. Despite the advanced age and disease progression, MRI
brain imaging and histopathological analyses indicated a reduction in total
NFT density, neuron loss, and ventricular enlargement. Collectively, these
findings indicate a strong association between the presence of NFTs and
cellular senescence in the brain, which contributes to neurodegeneration."

[https://doi.org/10.1038/s41586-018-0543-y](https://doi.org/10.1038/s41586-018-0543-y)

"Here we show a causal link between the accumulation of senescent cells and
cognition-associated neuronal loss. We found that the a mouse model of tau-
dependent neurodegenerative disease accumulates p16INK4A-positive senescent
astrocytes and microglia. Clearance of these cells as they arise using INK-
ATTAC transgenic mice prevents gliosis, hyperphosphorylation of both soluble
and insoluble tau leading to neurofibrillary tangle deposition, and
degeneration of cortical and hippocampal neurons, thus preserving cognitive
function. Pharmacological intervention with a first-generation senolytic
modulates tau aggregation."

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richk449
Haven’t lots of drugs shown promise in mice, but then failed in humans? Why is
this one different?

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ncmncm
Still no closer to a cause.

Recent successes with antivirals, and high correlation with bacterial
infection, should be getting the bulk of funding, but they are mostly still
puttering with plaques and tangles.

What will all the protein folding specialists do when it turns out to be a
virus or something?

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melling
That’s because research is incredibly underfunded:

[https://www.aarp.org/health/brain-
health/info-2015/alzheimer...](https://www.aarp.org/health/brain-
health/info-2015/alzheimers-research.html)

[https://www.alzheimers.net/2013-09-25/alzheimers-research-
fu...](https://www.alzheimers.net/2013-09-25/alzheimers-research-funding/)

A much larger amount of money has been put in HIV research over the past 25
years, for example, and great progress has been made.

Imagine an equal amount of funding for Alzheimer's over the past 25 years.

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ncmncm
That makes it the much more urgent not to squander it all on hypotheses that
failed 20 years ago.

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melling
Sure, they can move the small amount of funding to some other promising idea
for a decade until it sputters, then pick the next promising idea.

Considering the cost to society, we really need invest a lot more now. Then we
can look at several ideas in parallel, etc

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ncmncm
Increased funding tends to depend on success with what is being spent.
Spending more over the past two decades would have been throwing good money
after bad, so it is good it wasn't spent. Stewards of that spending have
demonstrated their foolishness, year in and year out.

The difficulty now is how to wrench control of such spending out of the hands
of those who squandered it. Probably the American and maybe European agencies
will find themselves unable, being fully captured.

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djohnston
i read somewhere that tau shows up first, and that amyloid may be a natural
response to the dysfunction caused by tau. tau is also implicated in several
other degenerative diseases that lack amyloid abnormalities, like CTE and FTD.
super interesting!

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dmix
> The injectable molecule binds to misfolded tau and releases a radioactive
> signal researchers can visualize via PET scans.

I just want to say that this is really cool. Biology is such a weird field to
work within.

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throwawayhhakdl
I’m no biomed expert. But I recall earlier discussions that amyloid plaque is
basically just misfolded proteins, which are hard to differentiate from prions
by any meaningful definition.

Now I have no idea what Tau proteins are, but it sounds like they’re also a
type of misfolded protein. So, to those more knowledgeable, how inaccurate
would to be to say Tau proteins are basically prions too?

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Terr_
> misfolded proteins, which are hard to differentiate from prions

Prions differ in that they are not merely misfolded, but they also catalyze
more of themselves.

