Fig. 5.

Schematic depiction of the genetic (top) and non-genetic (bottom) factors that are contributory to the complex, multi-stage pathologic cascades of neurodegenerative diseases. Different genetic factors may either contribute to “primary” condition-specific aspects of disease progression, or may induce pleiotropic effects that can influence (protect from, or exacerbate) misfolded proteins in multiple diseases, resulting in phenotypes that overlap in both clinical and pathological contexts. The aspects that may be most amenable to disease-specific therapeutic strategies are “upstream” influences, whereas the “downstream” pathologic manifestations correlate best with clinical symptoms