Herein, we systematically investigated the relationships of CSF complement proteins (C1q, C2, C5, C6, complement component C8 beta chain [C8B], and complement factor B [CFB]) with cognition, AD pathology, and brain structure from the AD Neuroimaging Initiative (ADNI) cohort, and further explored the potential mechanisms underlying the associations between CSF complement proteins and cognition. Here, CFB is linked to Alzheimer disease.