Figure 16.

Revised hypothesis of the ‘triggers, facilitators and aggravators’ for PD and AD pathogenesis. Our results are in accordance with the hypothesis proposed by Johnson et al.²⁴ and can be partially applied to both PD and AD pathogenesis. Our data obtained from human post-mortem brain samples staged in the aggravator phase show that autophagy is impaired in key areas, but we do not confirm cell-to-cell propagation of aggregated proteins, since SNCA aggregates only appear in the SNpc of PD patients and Aβ aggregates are only present in the hippocampus and cortex of AD patients. Our data also support that microtubule disassembly due to mitochondrial dysfunction, a proposed facilitator, prompts the onset of PD or AD symptoms and might trigger autophagic deficits that will exacerbate cell loss and neuropathology.