Systematic review summarizes complement system alterations in Alzheimer's disease pathogenesis and therapeutic potential

This systematic review synthesizes existing current evidence regarding complement system alterations in Alzheimer's disease. It does not present primary trial data but rather summarizes findings on pathogenesis and therapeutic implications. The broad comprehensive scope covers the biological mechanisms linking the immune system to neurodegeneration.

The authors describe dysregulation of the complement system as playing a critical role in Alzheimer's disease. This dysregulation links genetic risk, protein aggregation, neuroinflammation, and neurodegeneration. Text states aberrant activation contributes to excessive synaptic pruning and sustained inflammatory responses. These findings underscore the high biological plausibility of targeting this specific pathway.

Complement components have attracted attention as potential biomarkers and therapeutic targets. However, the review notes limitations in disease specificity. This uncertainty affects clinical utility despite the mechanistic interest. The authors highlight that while components are attractive, specificity remains a clear significant hurdle for implementation.

Therapeutic challenges include intervention timing, patient stratification, and blood–brain barrier delivery. The authors acknowledge these barriers alongside the limitations in disease specificity. Limited efficacy of amyloid-targeted therapies highlights the need for additional mechanisms. These practical hurdles suggest that translation to clinical practice requires further development and ongoing research.

Complement components have attracted attention as potential biomarkers and therapeutic targets. Clinicians should recognize the evidence remains observational in nature regarding these mechanisms. The review emphasizes the need for caution when interpreting these pathways as important definitive treatment strategies moving forward.