. Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4489-94. Epub 2015 Mar 23 PubMed.


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  1. This is a very interesting paper, which furthers the concept of "SOD1 strains" in ALS and mouse models of the disease. Infectious prions (CJD in humans, scrapie in sheep, BSE in cattle, and CWD in deer and elk) do not exist in one monolithic form, but rather can exhibit “strain behavior” in a particular species. In sheep scrapie, the first infectious prion passaged to mouse models, approximately 20 strains were cloned and defined on the basis of incubation time, brain regions predominantly affected, and biochemical features such as glycosylation preferences. It turns out that non-infectious prion-like agents causing common neurodegenerative diseases also exhibit strain behavior. For Alzheimer’s disease, strain properties of aggregated Aβ in human brains have been found to correlate with rate of progression of disease (Cohen et al., 2015). In Parkinson’s disease and in multiple systems atrophy, different strains of aggregated α-synuclein have been identified with different pathological activity on the aggregation of tau protein in cell lines in vitro (Guo et al., 2013) and on the vulnerable neuronal pool in human brain (Watts et al., 2013). Tauopathy has been found to propagate in at least two different strains (Ayers et al., 2014) that correspond to the clinical features and rate of progression in humans. And finally, at the end of last year, ALS SOD1 propagation joined the "strain concept" with the first transmissions of disease to a mouse model (Sanders et al., 2014)—G93A "seeds" transmitted differently than human in wild-type transgenic mice. Now the current article shows with great rigor that the propagating misfolding of D90A SOD1 in transgenic mice differs with regard to epitope exposure to G93A, G85R, and human wild-type SOD1.


    . Rapidly progressive Alzheimer's disease features distinct structures of amyloid-β. Brain. 2015 Apr;138(Pt 4):1009-22. Epub 2015 Feb 15 PubMed.

    . Distinct α-synuclein strains differentially promote tau inclusions in neurons. Cell. 2013 Jul 3;154(1):103-17. PubMed.

    . Transmission of multiple system atrophy prions to transgenic mice. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19555-60. Epub 2013 Nov 11 PubMed.

    . Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron. 2014 Jun 18;82(6):1271-88. Epub 2014 May 22 PubMed.

    . Experimental transmissibility of mutant SOD1 motor neuron disease. Acta Neuropathol. 2014 Dec;128(6):791-803. Epub 2014 Sep 28 PubMed.

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  1. Design From Disorder: New Test Reveals Different Strains of SOD1