在中国队列中，血清PF4水平降低与阿尔茨海默病的认知衰退及脑脊液生物标志物相关。

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

作者信息

Sun Hao, Chen Dong-Wan, Ma Yuan-Ye, Liu Bai, Wang Jun, Lai Yu-Jie, Zeng Gui-Hua, Shen Ying-Ying, Tan Cheng-Rong, Bu Xian-Le, Zeng Fan, Wang Yan-Jiang

机构信息

Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Department of Neurology, The General Hospital of Western Theater Command, Chengdu 610083, China.

Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

出版信息

Exp Gerontol. 2025 Mar;201:112689. doi: 10.1016/j.exger.2025.112689. Epub 2025 Jan 24.

DOI:10.1016/j.exger.2025.112689

PMID:39855320

Abstract

BACKGROUND

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).

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

血小板因子4（PF4）是一种从血小板α颗粒分泌的趋化因子，最近已被证明可减轻神经炎症并改善与衰老相关的认知能力下降，这可能与阿尔茨海默病（AD）有关。

目的

本研究旨在调查AD患者血清PF4水平的变化、血清PF4与脑脊液（CSF）中β淀粉样蛋白（Aβ）和tau水平之间的相关性，以及PF4在AD中的潜在诊断效用。

方法

进行了一项横断面研究，纳入38例淀粉样蛋白阳性的AD患者和50例认知正常的对照。使用人CXCL4/PF4酶联免疫吸附测定（ELISA）试剂盒检测血清PF4水平。通过市售试剂盒在全自动Lumipulse G1200平台上测量CSF中Aβ42、Aβ40、p-tau181和t-tau的水平。

结果

AD患者血清PF4水平显著降低（5163.51（3198.24 - 6301.15）对5859.29（4126.06 - 8006.70），Z = -2.30，P = 0.021）。在多线性回归分析中，调整年龄、性别、APOE ε4状态、血小板计数、血小板分布宽度（PDW）和血脂异常合并症后，AD诊断与PF4水平之间的负相关性仍然存在（β = -1972.292，P = 0.009）。进一步分析表明，血清PF4水平与CSF Aβ42水平和简易精神状态检查表（MMSE）评分呈正相关，与CSF t-tau水平呈负相关。此外，血清PF4对AD的曲线下面积（AUC）（AUC = 0.6437，P = 0.022）与CSF Aβ40的曲线下面积（AUC = 0.6400）相当，但低于CSF Aβ42、p-tau181和t-tau的曲线下面积。当分别将血清PF4与其他CSF AD生物标志物联合使用时，AUC略有增加。