There has been an explosion in the number of papers discussing the hypothesis of 'pathogenic spread' in neurodegenerative disease — the idea that abnormal forms of disease-associated proteins, such as tau or α-synuclein, physically move from neuron to neuron to induce disease progression. However, whether inter-neuronal spread of protein aggregates actually occurs in humans and, if so, whether it causes symptom onset remain uncertain. Even if pathogenic spread is proven in humans, it is unclear how much this would alter the specific therapeutic approaches that are in development. A critical appraisal of this increasingly popular hypothesis thus seems both important and timely.
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The authors thank C. Masters, R. Ridley and S. Bradner for sharing unpublished results, and S. Brandner, P. Brundin, B. Caughey, J. Collinge, D. Harris, O. Isacson, J. Kordower, V. O'Connor and H. Perry for discussions. This work was support by grants from the US National Institutes of Health to D.M.W. (AG046275 and AG047505) and D.J.S. (AG06173 and NS083845).
The authors declare no competing financial interests.
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Walsh, D., Selkoe, D. A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration. Nat Rev Neurosci 17, 251–260 (2016). https://doi.org/10.1038/nrn.2016.13
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