Decreased serum PF4 levels correlate with cognitive decline and CSF biomarkers in Alzheimer's disease in a Chinese cohort

Platelet factor 4 (PF4), a chemotactic factor secreted from the α-granules of platelets, has recently been proved to mitigate neuroinflammation and improve aging-related cognition decline, which may be involved in Alzheimer's disease (AD). This study aims to investigate the alterations of serum PF4 levels in AD, the correlation between serum PF4 and β-amyloid (Aβ) and tau levels in cerebrospinal fluid (CSF), and the potential diagnostic utility of PF4 in AD. A cross-sectional study was conducted involving 38 amyloid-positive AD patients and 50 cognitively normal controls. The levels of serum PF4 were detected using the Human CXCL4/PF4 enzyme-linked immunosorbent assay (ELISA) Kit. The levels of CSF Aβ42, Aβ40, p-tau181, and t-tau were measured on the fully-automated Lumipulse G1200 platform via commercially available kits. The levels of serum PF4 were significantly decreased in AD patients (5163.51 (3198.24-6301.15) vs. 5859.29 (4126.06-8006.70), Z = -2.30, P = 0.021). The negative correlation between AD diagnosis (β = -1972.292, P = 0.009) and PF4 levels retained after the adjustments of age, sex, APOE ε4 status, platelet count, platelet distribution width (PDW), and comorbidity of dyslipidemia in the multiple linear regression analysis. Further analysis showed that serum PF4 levels were positively correlated with CSF Aβ42 levels and Mini-Mental State Examination (MMSE) scores, and negatively correlated with CSF t-tau levels. Besides, the area under the curve (AUC) of serum PF4 for AD (AUC = 0.6437, P = 0.022) was comparable to that of CSF Aβ40 (AUC = 0.6400) yet lower than those of CSF Aβ42, ptau181, and t-tau. The AUC slightly increased when combining serum PF4 with other CSF AD biomarkers separately. The serum levels of PF4 were decreased in AD patients and were significantly correlated with the cognitive function and CSF levels of Aβ42 and t-tau. PF4 may become a promising anti-aging and therapeutic target for AD, which is worthy of further study.