Figure 1. Appraising the Braak hypothesis as the mechanistic basis for cognitive decline in Parkinson’s Disease.

The literature supports cell-to-cell transfer of aSyn from affected to pathology-naïve cells and the subsequent ability of pathologic aSyn to cause templated misfolding of endogenous aSyn in a prion-like manner. However, disconnects emerge with respect to whether aSyn pathology always forms the basis for neuronal dysfunction and cognitive impairment, and whether aSyn pathology consistently follows a rostro-to-caudal spread pattern in the human brain.