

Like a prion, Alzheimer's protein seeds itself in the brain  - rfreytag
http://www.sciencenews.org/view/generic/id/341619/title/Like_a_prion%2C_Alzheimers_protein_seeds_itself_in_the_brain

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rcthompson
Incidentally, if you're wondering why this kind of stuff only seems to happen
in the brain, in broad terms the answer is this: almost every other cell type
in your body has the luxury of committing suicide (technical term: apoptosis)
and being replaced by other cells of the same type which are growing and
proliferating. For example, if a virus infects one of your intestinal
epithelial cells, that cell can trigger it's self-destruct signal pathway (or
a cytotoxic T-cell can trigger it externally) and initiate programmed cell
death, thereby containing the infection (note that apoptosis functions to
effectively demolish the entire contents of the cell, not just tear it apart
and release whatever is inside).

In contrast neurons generally do not proliferate much after you're born
(there's some debate about this, but even so a particular neutron is valuable
because of the connections it has made, which are irreplaceable), so having
each neutron kill itself when something goes bad would shortly leave you
without a functioning nervous system. So neurons have to resort to more
"creative" measures to clean up problems without destroying their entire cell
bodies (e.g. autophagy, in which the cell cordons off a part of itself and
then digests it). Naturally, these mechanisms are not as effective as
demolishing the entire cell, so some problems can arise that neurons can't
handle. But they are programmed not to kill themselves under almost any
circumstances, so they continue limping along with only partial functionality
or none at all.

~~~
arvinjoar
Does any flagging take place in the brain at all? I have tried to keep up to
date on Alzheimer's without knowing much about the human body. One thing I've
thought about given the debate over whether Aβ is _the_ culprit, one of many
culprits, or just a visible sign of Alzheimer's got me thinking about it as a
flagging mechanism. If a synapse is dead or in some way misbehaving it might
be good to flag it as "corrupted", might that be what Aβ is doing at all? I
mean system-wise it makes sense, but I know way too little about the human
body or the brain.

~~~
rcthompson
There are lots of "damage-sensing" mechanisms at all scales within the body.
These are how your skin knows to grow after an injury, how your immune system
detects which cells are infected and need to be killed, and how your cells
know which parts of themselves to digest via autophagy, among other things. At
the single-protein level, there's ubiquination, which marks protein molecules
for destruction, either because they are misfolded, damaged, or no longer
needed. But this doesn't work when those misfolded proteins clump together
into plaques. Then you need something like autophagy. But even that has
limits, and a cell that lives for decades tends to reach those limits.

As for Aβ possibly being the body's way of flagging problem areas, that seems
unlikely, because such a function probably would not involve drastically
changing its 3-D structure (i.e. going from "correctly folded" state to
"misfolded" state), and certainly would not involve forming plaques. These and
many other observed features are better explained as features of the pathology
and not just a kind of damage signal reporting on the existence of a problem.

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raintrees
I am definitely no medical expert - Are we sure Alzheimer's is not a causal
result of consuming prions (BSE or CJD)?

~~~
rcthompson
I believe that Alzheimer's has different clinical presentation than either BSE
and CJD, and that the misfolded protein being blamed for Alsheimer's is a
different protein than those blamed for the other two diseases.

~~~
einhverfr
Additionally we know that there are some prion diseases that are not
consumption-related. Fatal familial insomnia for example.....

