C3 and Alzheimer disease: BBB disruption is a hallmark of neurodegenerative diseases, containing AD, Parkinson's disease, Amyotrophic lateral sclerosis, Multiple Sclerosis, and Huntington's disease.[46] As we known, aging‐ or external factor‐driven systemic inflammation and oxidative stress can lead to the BBB degradation and dysfunction.[46, 47] Therefore, if BBB has been disrupted by these factors, peripheral C3 proteins could theoretically cross the brain and increase the risk of those neurodegenerative diseases.