Since the coagulation and complement cascades are associated with BBB dysfunction and AD pathology, we investigated the expression changes of coagulation (fibrinogen alpha chain-FGA, coagulation factor XIII A chain-Factor XIIIα) and complement (plasma protease C1 inhibitor-C1-INH, Complement component 3-C3) factors in the brain of novel AD model (APP23) mice with CCH at 12 months of age.
Plasma clusterin level showed an association with overall AD polygenic risk score, while clusterin, C1inh, and CRP levels each displayed some association with the inflammatory-specific AD polygenic risk score.
Since IFN-gamma is apparently lacking in the brain parenchyma, and amyloid plaque-associated cytokines (IL-1beta, IL-6, TNF-alpha) do not stimulate C1-Inh expression in vitro, the nature of the stimulus responsible for neuronal C1-Inh expression in AD brains remains to be investigated.