
How an outsider bucked prevailing Alzheimer's theory, clawed for validation - dogan
https://www.statnews.com/2018/10/29/alzheimers-research-outsider-bucked-prevailing-theory/
======
rpedela
One of things I like about the Howard Hughes Medical Institute (HHMI) is that
they find great scientists and just fund them. The scientists can research
whatever they want as long as they keep producing. I always wondered if a
hybrid approach to funding would work well at the government level. The
current, permission-based process would remain in place for new researchers to
prove themselves, and then an HHMI-style process for researchers who have
proven themselves. There would be checks in place and if the funded
researchers stop performing then they have to go back to the normal process.
There are several details that would have to be worked out to guard against
politics, etc. I think this may overcome the government agencies tendency to
reject truly new ideas especially when they contradict the prevailing theory.

~~~
WalterBright
Reminds me of Lockheed's Skunkworks. I've heard lots of businessmen say
they're going to recreate skunkworks, but with improvements.

The improvements, of course, make it not a skunkworks and these efforts never
deliver skunkworks performance.

Could the government create a skunkworks? Not likely, because they fought
against Kelly Johnson constantly over how he ran it.

I bet Paul Allen could have done it, because he had a track record of funding
competent people and letting them do what they wanted.

~~~
iscrewyou
I’m in the midst of listening to the Skunk Works audiobook. And it’s
fascinating. It had been on my list of things to read but I just couldn’t
wait. I bit the bullet and bought the audiobook. It’s worth every penny.

~~~
Lutzb
The book by Leo janos?

~~~
iscrewyou
Yes, him and Ben R. Rich.

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neuromantik8086
This isn't a particularly surprising story considering the history of science.
To give an example of how this sort of thing played out historically, Marshall
Nirenberg was basically persona non grata (or at least dutifully ignored) at
many scientific conferences prior to his postdoc's discovery of the codon for
phenylalanine. At the time, he was working at the NIH, which was considered
very low prestige by many contemporary scientists. Somewhat fortuitously,
Francis Crick heard a lecture by Nirenberg at a conference in 1961 and
considered it good enough to bring to the attention of the other key players
of the day, and Nirenberg was elevated from obscurity to stardom. For whatever
reason, Nirenberg's postdoc never really achieved stardom, despite being the
individual who _actually_ made the discovery.

For more information:

[https://www.telegraph.co.uk/news/science/science-
news/854683...](https://www.telegraph.co.uk/news/science/science-
news/8546830/Genes-and-DNA-meet-the-first-man-to-read-the-book-of-life.html)

~~~
DoreenMichele
Semmelweis was literally thrown into an insane asylum and died not long after,
following a beating by the guards. Einstein worked in a patent office, unable
to get a university job like he wanted until after his theory was proven
correct. It took years to get the evidence he needed.

[https://en.m.wikipedia.org/wiki/Ignaz_Semmelweis](https://en.m.wikipedia.org/wiki/Ignaz_Semmelweis)

------
DoreenMichele
Amyloid-beta is associated with sleep deprivation. This new research could
suggest that sleep is an essential component of the immune system.

 _If so, then the plaques it forms might be the brain’s last-ditch effort to
protect itself from microbes, a sort of Spider-Man silk that binds up
pathogens to keep them from damaging the brain. Maybe they save the brain from
pathogens in the short term only to themselves prove toxic over the long
term._

I really like the thinking here.

Similarly: In people with CF, calcium and glutathione build up in the cells.
High levels of calcium are associated with cell death, so much of the CF
community believes calcium is harmful.

I believe the calcium and glutathione are desperate efforts to buffer the cell
in the face of deranged cell chemistry. I believe the high calcium is
indicative of other things being really bad and the body trying desperately to
compensate.

If this guy wants another outside-the-box research project, there you go. I
would love to see that looked into.

Edit: Is it me, or does the article actually switch from saying _amyloid-beta_
to saying _beta-amyloid_ midway through?

 _This month, however, he got an unheard-of email from NIH: The agency had
found some extra money lying around in its budget. Would he please respond to
the reviewers and resubmit his proposal? An over-the-moon Moir did. He expects
to hear back in a few weeks._

Yay! I hope he gets it.

~~~
cbkeller
That's really interesting. The correlation of amyloid plaques and alzheimers
has always seemed to me like a classic case of the ambiguity of correlation
and causality (i.e., cause or symptom?!). Sounds like the same deal with
calcium in CF

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eganist
This seems to be referencing the path to mainstream exposure for the
infectious theory of Alzheimer's. Prior discussions (not the same link) on HN,
posted for reference because they touch on the past research that was
previously posted here:

[https://news.ycombinator.com/item?id=18306381](https://news.ycombinator.com/item?id=18306381)
(this one's a comment I made associating the cortisol/Alz risk to the
microbial Alz connection; it's nothing more than a hypothesis)

[https://news.ycombinator.com/item?id=17446016](https://news.ycombinator.com/item?id=17446016)

[https://news.ycombinator.com/item?id=17540512](https://news.ycombinator.com/item?id=17540512)

[https://news.ycombinator.com/item?id=17540094](https://news.ycombinator.com/item?id=17540094)
(this is the parent link for the antiviral risk reduction study -- a good
read, comments and source article)

There's a decent amount of reading when scholar-googling:

[https://scholar.google.com/scholar?q=hsv1+alzheimers](https://scholar.google.com/scholar?q=hsv1+alzheimers)

Moir's paper specifically: the relationship between β-Amyloid and viruses in
the brain:

[https://www.cell.com/neuron/fulltext/S0896-6273(18)30526-9](https://www.cell.com/neuron/fulltext/S0896-6273\(18\)30526-9)
(study link)

There's also research pointing to sleep's function as helping clear out
plaques such as beta-amyloid.

[https://news.ycombinator.com/item?id=16026655](https://news.ycombinator.com/item?id=16026655)

Finally, there's at least a bit of research pointing to boosted susceptibility
of herpes viral infections when carrying ApoE4:

[https://scholar.google.com/scholar?q=hsv1+apoe4](https://scholar.google.com/scholar?q=hsv1+apoe4)

The novel conclusion from all of this, which I suspect is being actively
investigated, is that there's a potentially complicated interplay of an
enhanced viral infection (HSV/HHV enabled by ApoE4) + evolutionary defense
going into overdrive (β-Amyloid) + (potentially) sleep deprivation keeping the
body from clearing out the residue -> disease.

\---

I'm particularly motivated to track this research because of its prevalence in
my family background and because, from what I can tell, I've thus far managed
to avoid the environmental trigger-pull. I can already tell you I'll probably
go on (val)acyclovir lifetime if I'm ever diagnosed with any particular
strain, as it looks like active infection, with outbreaks, is what's likely to
act as the first domino to tip.

~~~
stephengillie
From a previous discussion, beta-ameloyd isn't well studied, but it appears to
be a viral catch-all, attaching to many viruses. The reason herpes is so
significant is because it uses time-release capsules to continually reinfect a
host user, and continually caught in the beta-ameloid. So herpes sufferers
have more beta-ameloid to clear away most nights.

~~~
eganist
Yup. Working thread here:

[https://news.ycombinator.com/item?id=18306921](https://news.ycombinator.com/item?id=18306921)

(between you and me, incidentally.)

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subcosmos
This all makes sense. APOE literally carries viruses around the body :
[https://bit.ly/2oRVFSr](https://bit.ly/2oRVFSr)

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ironic_ali
> Complaints about being denied NIH funding are as common among biomedical
> researchers as spilled test tubes after a Saturday night lab kegger.

Comedy in science writing?

------
pasta1212
> Complaints about being denied NIH funding are as common among biomedical
> researchers as spilled test tubes after a Saturday night lab kegger

Is this supposed to mean complaints are common?

~~~
stephengillie
The article is littered with references to beer. As though the target
demographic alcoholics who enjoy PopSci.

~~~
neuromantik8086
Scientific / conference culture has a somewhat concerning relationship with
alcohol, which was a contributing factor to my ultimately leaving science. The
amount of pressure to go out to a pub with your colleagues was much higher for
me than it was in my current job, in large part because serious discussions
and informal deals that could directly impact your academic career tend to
happen in these sorts of contexts. I suspected that a lot of my co-workers in
science were high functioning alcoholics.

