Transmission of Alzheimer’s disease in humans

Life is the mode of existence of protein bodies… It is precisely the most essential vehicle of cell-formation, protein, that decomposes first of all, and so far it has never been built up again.

                                  Dialectics of Nature. Frederick Engels (1883)

To perform their functions,  proteins have to keep up a correct structure. An incorrect structure due to a mutation or environmental damage leads to protein misfolding and aggregation. Imagine that you are making a butter for pancakes. A good butter is smooth, but if you mix it incorrectly it is full of annoying hard little lumps, composed of undissolved flour. Now, “butter” is you normal protein state, while “nubbins” – incorrectly folded protein, which form aggregates.

Currently, we are experiencing an epidemic of “misfolded protein diseases”. Misfolded proteins accumulate as “inclusions” or “plaques”, causing pathologies of nervous systems such as Creutzfeldt–Jakob disease (CJD) or Alzheimer’s disease.

A  stained slice of  brain of a CJD sufferer. Note large white spots where the cells were killed by accumulation prion. Also note long “strings”, this is accumulated prion made of PrP protein. Image by Dr. Al Jenny via Wikimedia Commons.

The misfolding of a protein called PrP causes Creutzfeldt–Jakob disease. Ten years ago, there was a consensus that  CJD and other prion diseases were the only ones caused by a “protein-only infectious particles”  (prions). Prion diseases transmit between species and people via for example eating raw meat or, in case of humans, transfusion of contaminated protein medical products.  The misfolded PrP converts the normal copy of the protein molecule into the pathological form.

Alzheimer’s disease develops mostly after the age of 65 as a result of accumulation of a misfolded protein called Aβ. Alzheimer’s disease, previously thought as localised, “dead end” pathology was eventually transmitted in primates and rodents after inoculation with diseased brain tissue. However, there is gap between infecting animals in artificial conditions and proving that  Alzheimer’s transmits between humans.

The prions were unknown before 1990th and as a result 200 patients treated with human growth hormone contaminated with prion developed CJD and died. The article by Zane Jaunmuktane et al.  found that tissue samples from eight patients out of  200 also accumulated Aβ plaques – the hallmark of Alzheimer’s disease.  The plaque accumulation is unusual for these relatively young  people (the patients were 36-51 years old) or their genetics (they didn’t have gene variants, which predispose to the Alzheimer’s development).

116 patients with other prion diseases did not show Alzheimer’s pathology. In their tissues slices , the Aβ plaques did not overlap PrP deposits. Formation of independent aggregates a parallel transfer of  Aβ with the particular hormone prep, rather than cross-seeding of misfolded Aβ and PrP. So the case sounds like co-infection with  hepatitis virus   and HIV, which also were transferred via contaminated blood products before the tests for HIV. 

A slice of stained brain tissue of Alzheimer’s patient. Triangular elongated cells are neurons. Round circles are Aβ  plaques. Image by KGH from Wikimedia Commons.

The article confirms an emerging consensus that despite their differences, “misfolded protein diseases”, including CJD and Alzheimer’s, have the same mechanisms of development and propagation. The epidemic of prion diseases predicted after the UK outbreak of the 1980s and 1990s failed to materialise and the governments withdrawn money for prion research. But the precautionary measures  against these diseases may have been limiting the spread of other, more common misfolded protein diseases.

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One thought on “Transmission of Alzheimer’s disease in humans

  1. Pingback: Why do we bury our dead: transmissible Alzheimer’s revisited | Go Yeast

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