Figure 1

Potential modes of comorbidity. In neurodegenerative disorders there are protein insults considered imperative to the development and characterization of a specific disease (hallmark lesion A) and additional protein pathology that is traditionally classified to another disease state (hallmark lesion B). There are several potential mechanisms by which cross-talk may be occurring between these separate lesions to result in comorbidity: i) at the level of the initial pathogenic signalling cascades which results in the formation of seeds A and B, respectively, (ii) through the ability of one pathological protein (which could range from a post-translational modification state through to a mature aggregate) to induce pathological changes in the state of a protein implicated in another disease, which may also lead to the formation of mixed aggregates, and (iii) a convergence onto mutual cell death pathways.