Plasma Fibrinogen Correlates with Aβ Clearance of monocytes and AD Biomarkers in Cognitively Normal Individuals

Impaired peripheral clearance of amyloid-β (Aβ) contributes to Alzheimer's disease (AD) pathogenesis. Monocytes play a key role in this process, but their function declines with aging, is further impaired in AD. Fibrinogen, an acute-phase protein elevated in aging and AD, can bind monocyte integrin receptors and potentially alter their function. However, whether fibrinogen correlates with Aβ clearance of monocytes and plasma AD biomarkers in cognitively normal adults remains unknown. To investigate the association between plasma fibrinogen levels, monocyte counts, uptake of Aβ42 by monocytes, and plasma AD-related biomarkers (Aβ42, Aβ40, T-tau) in cognitively normal older individuals. In this cross-sectional pilot study, 25 cognitively normal participants were enrolled. Plasma AD biomarkers were measured using SIMOA. Peripheral blood mononuclear cells were isolated, and monocytic uptake of FITC-labeled Aβ42 was assessed by flow cytometry. Partial correlation analyses were performed, adjusting for age, sex, vascular risk factors, and APOE ε4 genotype. After adjusting for confounders, plasma fibrinogen levels were significantly positively correlated with Aβ42 (γ = 0.616, P = 0.005), the Aβ42/Aβ40 ratio (γ = 0.478, P = 0.038), and T-tau (γ = 0.544, P = 0.016), and negatively correlated with monocyte count (γ = -0.479, P = 0.038) and uptake of Aβ42 by monocytes (γ = -0.569, P = 0.011). In cognitively normal individuals, higher plasma fibrinogen is associated with impaired Aβ clearance of monocytes and elevated plasma AD biomarkers, suggesting that fibrinogen-related monocyte dysfunction may represent an early peripheral event in the AD continuum.