

An Outcast Among Peers Gains Traction on Alzheimer's Cure  - cwan
http://online.wsj.com/article/SB10000872396390443624204578060941988428604.html?mod=WSJ_MIDDLENexttoWhatsNewsSecond

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pygy_
This is fascinating.

I've been following, at a distance, the developments of AD research.

The culprit is not Amyloid or Tau in themselves, but their misfolded variants,
which have prion-like properties: they can't be degraded (and thus
accumulate), and turn their respective healthy variants into their
pathological counterparts.

Misfolded Tau is intracellular, but it is known to propagate from cell [0,1],
causing havoc on its way since its accumulation is sufficient to cause
neurodegeneration.

Misfolded Amyloid may not be toxic in itself, but it probably acts as a
misfolding template for Tau (it does in vitro) [2].

\--

0\. <http://www.ncbi.nlm.nih.gov/pubmed/22365544>

1\. <http://www.ncbi.nlm.nih.gov/pubmed/19282288>

2\. <http://www.ncbi.nlm.nih.gov/pubmed/22965142>

These may not be the best sources for these very points they're the first
relevant papers I could find on the spot.

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Daniel_Newby
The Alzheimer's prion hypothesis is implausible, or at least incomplete. The
proteins should spontaneously misfold at a small rate, followed by dementia
20-30 years later. The incidence at age 90 is something like 50%, and if we
follow the exponential curve backwards, something like 0.5% of newborns should
have tau prions, meaning several percent of teenagers should have early
dementia. Instead the teenage dementia rate is vanishingly low, effectively
zero.

We would also expect clusters of Alzheimer's disease in young patients who
were seeded by tissue contamination: recreational IV drug use, transplants,
blood transfusions, etc. We do not observe this.

The only obvious factor seems to be age. Something changes during aging that
enables Alzheimer's disease. Before the change we are essentially bulletproof.
After a steady increase sets in. I'm betting on some hormone being the
culprit, possibly tied to a reactivated virus.

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pygy_
Most interesting, thanks for the insight. I'd rather go for incomplete, then,
since the evidence for tau neurotoxicity is there.

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kiba
_History is peppered with examples of scientists who struggled against a
prevailing orthodoxy, only to be proved right._

This may be right, but it's also an argument used by crackpot theorists.

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andrewflnr
The point is, that having to struggle against the mainstream is not strong
evidence in either direction. The difference is, the crackpots don't have any
other strong evidence, either.

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nitrogen
_"Science is politics," he says. "And the politics of amyloid won."_

This quote is _just_ the kind of thing the public need to read to improve
their confidence in the scientific method.

There needs to be a better distinction between established scientific
knowledge and the funding decisions for research of unresolved questions. In
other words, Science HAS_A Politics, not IS_A Politics.

~~~
ams6110
Scientific research requires money, and there is no money without politics.

~~~
nitrogen
But politics and money typically do not dictate scientific results, as
evidenced by the failure of the amyloid-targeted trials mentioned in the
article.

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tocomment
So how does this fit in with the type 3 diabetes idea that's been floating
around reddit lately?

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kiba
Why would you say that if the article didn't even mention diabetes?

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gstamp
Because some believe alzheimer's is another form of diabetes. [1]

1\. [http://opinionator.blogs.nytimes.com/2012/09/25/bittman-
is-a...](http://opinionator.blogs.nytimes.com/2012/09/25/bittman-is-
alzheimers-type-3-diabetes/)

