[qCOVET]

Very interesting - thank you for sharing.

Summary for others:

Protein misfolding and aggregation inside the cell was known to contribute to Alzheimers. This article points to the possibility of misfolded and aggregated proteins of Alzheimer patients triggering (or seeding) misfolding and aggregation of otherwise 'healthy' proteins in non-alzheimer patients. Much like the mad cow disease.

[evoloution]

To save you guys a lot of time (years of reading an artifact-infested literature), let me give you my 5 cents.

The fact that a misfolded protein can lead to aberrant protein aggregation is known for many years and is certainly true for CJD (a big discovery). It is not the first time that people try to pitch the idea that AD is a prion disease.

Apart from a few very powerful individuals in the field, most scientists believe that the amyloid depositions DO NOT CAUSE the disease, but maybe they are a part of the pathophysiological process (immuno response?). Some facts: -Do you see the depositions in healthy individuals? Yes (but fewer mostly in certain areas of the brain) -Do the levels of the amyloid deposition correlate with the degree of dementia? No concensus -Do amyloid deposition in vitro induce neurodegeneration or abnormal electrophysiology? No -Have all drugs so far with published data of phase III clinical trials based on the amyloid hypothesis failed? Yes (maybe the last one not miserably)

But the problem is that the amyloid cascade hypothesis is at this point the only working hypothesis for AD and people do not want to lose their grant money or positions in pharma and go back to begin from scratch to find what is really causing AD.

Source: I work in AD research.

[qCOVET]

Thank you. Great answer!

I vaguely remember from my academia days that there was another protein of immense interest that led to centrosomal aggregation of proteins - a precusor to Alzhemier and it was called something like - alpha-synuclein. Is that a subset of amyloid family ? or different ?

[jjoonathan]

Are CJD and Alzheimer's two names for the same thing, just with different mechanisms of transmission and initial loads?

(I walked away from a protein misfolding seminar with the vague impression that this was the case but I never managed to track down someone who knew enough to answer.)

[sp332]

They are different, but related. Some symptoms of CJD can be similar to symptoms of other progressive neurological disorders, such as Alzheimer’s or Huntington’s disease. However, CJD causes unique changes in brain tissue which can be seen at autopsy. It also tends to cause more rapid deterioration of a person’s abilities than Alzheimer’s disease or most other types of dementia.

[adenadel]

Current understanding is that they are two different diseases, but this paper hints that Alheimer's could possibly be caused by the misfolded prion present in CJD. The mechanism of CJD is fairly well understood while the mechanism(s) of Alzheimer's are more out in the open. Someone else could probably confirm with more confidence than I can.

[tilt_error]

Which indicates that Alzheimer is caused by prions as well?

[jjoonathan]

The idea that clumps of proteins misfolded into stacked beta sheets (beta amyloid plaques, i.e. Alzheimer's) tend to cause other proteins to misfold into beta sheets and join the glob. So, exactly like a prion except with a "messier" mechanism that doesn't strictly follow A+B->B+B.

Which raises the question: did prion diseases ever really strictly follow A+B->B+B? Can Alzheimer's be transmitted by eating "infected" brain tissue? If the answers are "No" and "Yes", then it seems that what we mistook for two diseases (because of differing context and symptoms) was actually one underlying mechanism (with different context and symptoms).

Disclaimer: I Am Not An Epidemiologist, I am not extensively familiar with recent literature on the subject, I just did a bit of unrelated work in computational protein folding and couldn't help but wonder.