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Protein Misfolding Disorders… is Alzheimer’s Contagious? September 23, 2006

Posted by Hegemony in Health, Science.
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Correct protein folding is a basic element of biological function. Misfolded proteins cannot perform their intended function but are usually corrected by chaperone proteins. In protein misfolding disorders (PMDs) these irregularities are not corrected and the proteins aggregate causing disease. Noted PMDs are Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, cystic fibrosis, and type II diabetes. There is also the well known subclass known as transmissible spongiform encephalopathies (TSEs). Among these are Bovine Spongiform Encephalopathy (“mad cow” or BSE), Scrapie, and Creutzfeldt–Jakob disease.

There is now sufficient evidence to support the theory that misfolding and aggregation of proteins is the basis for most PMDs. Abnormal protein aggregates are found in the tissues most damaged and accumulation of these aggregates is the accepted endpoint for PMDs.

We know that prion diseases (specifically TSEs) are transmissible. However, it took quite some time for the now accepted “protein only” hypothesis to gain a foothold. It seems to go against what we know about disease. These diseases involve the PrP gene which is found in all mammals. The normal cellular form of the protein is termed PrPc. A conformational change in this protein replaces many of the alpha helices with beta sheets. This modified form is called PrPsc. This protein seems to have the ability to cause disease by modifying PrPc creating more PrPsc. A study clearly showed that PrPsc is capable of modifying PrPc in vitro and that that infective PrPsc can cause disease when injected into hamsters. It should be noted that the hamsters were exposed to whole brain homogenate from the original sample so the purity of the sample cannot be guaranteed.

It is believe that these prion proteins begin catalyzing the conversion of PrPc like a crystal, producing long fibrils. These could eventually break into smaller segments either by mechanical force or an unknown enzymatic process. This is often referred to as the seeding-nucleation model and has become widely accepted.

It has long been in question if other PMDs can be transmitted like prion diseases. It seems that those who work with people suffering from PMDs do not have a higher chance of getting the disease themselves. However, the same is true for those who work with prions. The gestation period is also prohibitively long to study the effects of these factors. In addition to this limitation most PMDs are exclusively human diseases. Therefore, finding a suitable experimental model is difficult. Marmosets injected with brain homogenate from Alzheimer’s patients developed scattered amyloid plaques in a few months. However, it is not possible to guarantee that these were not all original plaques from the homogenate. A separate study failed to produce similar results in primates. Recent studies using transgenic mice expressing the human version of the amyloid precursor protein were injected with Alzheimer’s brain homogenate and developed significant amyloid plaques in several weeks. These mice develop plaques later in life by design so the true implications of this are questionable.

The best evidence for prion like activity in PMDs is in the case of systemic amyloidosis. In this disease an inflammatory response causes serum amyloid-A (SAA) protein to be deposited in various organs causing damage. This can be triggered in mice by eliciting an inflammatory response. The progression of the disease is increased dramatically with exposure to spleen or liver extract containing amyloid plaques. Additionally, study of mouse senile amyloidosis shows that oral administration of amyloid fibrils can cause the development of severe amyloid plaques.

With our knowledge of protein related diseases expanding rapidly some things we learn can be disconcerting. It may be possible for PMDs to be transmitted in some instances. Further studies are certainly required before any of them are labeled infectious.

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Comments»

1. prion - May 15, 2008

[...] fall into this non-prion category like Parkinson’s and Cystic Fibrosis. This article is a reviewhttp://hegemony.wordpress.com/2006/09/23/protein-misfolding-diseases-is-alzheimers-contagious/prion — Britannica Online EncyclopediaBritannica online encyclopedia article on prion: an abnormal [...]

2. Hegemony - May 15, 2008

I’m not sure what that comment was supposed to be about. Are you trying to point out that Parkinson’s isn’t a prion disorder? Because I clearly differentiated between misfolded proteins and prions.

3. LuLu - May 13, 2009

Is Alzheimers contagious???

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