A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration

There has been a surge in the number of papers discussing the idea that inter-neuronal spread of 'pathogenic' proteins contributes to neurodegenerative disease progression. Walsh and Selkoe provide a critical overview of the evidence for this mechanism, identify gaps in our knowledge and suggest experimental approaches to test the hypothesis. 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.