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This mechanistic hypothesis proposes a role for the Classical complement cascade in neurodegeneration. Evidence supporting this framework includes research demonstrating relationships between inflammation and neurodegeneration in Parkinson's disease (PMID 33182554), as well as work identifying CD38 involvement in neurodegeneration and neuroinflammation (PMID 32085567). However, this hypothesis is subject to ongoing scientific debate; for instance, systematic review evidence examining Mediterranean diet adherence, gut microbiota, and Alzheimer's or Parkinson's disease risk presents evidence that complicates certain aspects of inflammation-related neurodegenerative hypotheses (PMID 35144237). Scientific uncertainty remains regarding the precise mechanistic relationships between complement cascade activity and neurodegenerative disease progression.