It seems that the the Plasminogen system might have implications for neurodegenerative disorders and cognitive decline in general. Plasminogen/Plasmin is a protease that can break down alph-synuclein (Parkinson's), Tau (Dementia), Huntingtin (Huntington's Disease), and beta-Amyloid (Alzheimers). Plasmin activation also seems to improve the "glymphatic system", which is our brain's natural waste flushing system. Interestingly. the plasminogen system seems to be impaired in all of these diseases and might be a new direction for therapy.

The only problem is that plasmin/plasminogen seems to have a narrow therapeutic window since it also breaks down blood clots when outside the brain. I wonder if there is a selective plasmin mimetic or activator that exists so that its action is limited to the brain? This method would clear whatever defective proteins are causing the cognitive decline (and keep them from causing disease progression) and pave the way for other therapies to repair the damage; such as anti-neuroinflammatory drugs and thing that promote neurogenesis/synaptogenesis.

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IDK, I could be completely wrong about all this, but it seems like its an overlooked system.

Some Research:

https://www.ncbi.nlm.nih.gov/pubmed/25454795

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694579/

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092416