Background: It has been suggested that circulating Paraoxonase-1 (PON1) and apolipoprotein A1 (APOA1), which closely interacts with the antioxidant enzyme, could be implicated in Alzheimer’s disease (AD) and vascular dementia (VaD) development. This study aimed to evaluate PON1 changes in serum and cerebrospinal fluid (CSF) as evidence for its association with AD or VaD. Methods: Serum PON-arylesterase activity was measured in patients with AD, VaD, and CONTROLS distributed in two cohorts: Ferrara cohort (FC: n = 503, age = 74 years) and Amsterdam Dementia cohort (ADC: n = 71, age = 65 years). In the last cohort, CSF PON-arylesterase, CSF β-amyloid1-42, p-tau and t-tau, and imaging biomarkers were also measured. Results: AD and VaD patients of FC showed significantly lower levels of serum PON-arylesterase compared to CONTROLS, but this outcome was driven by older subjects (>71 years, p < 0.0001). In the younger ADC, a similar decreasing (but not significant) trend was observed in serum and CSF. Intriguingly, PON-arylesterase per APOA1 correlated with t-tau in AD group (r = −0.485, p = 0.002). Conclusion: These results suggest that decreased peripheral PON-arylesterase might be a specific feature of older AD/VaD patients. Moreover, we showed that PON-arylesterase/APOA1 is inversely related to neurodegeneration in AD patients, suggesting a prognostic usefulness of this composite parameter.

中文翻译：

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阿尔茨海默氏病和血管性痴呆患者血清和脑脊液中对氧磷酶-1的芳基酯酶活性。

背景：有人提出与抗氧化酶密切相互作用的循环对氧磷酶-1（PON1）和载脂蛋白A1（APOA1）可能与阿尔茨海默氏病（AD）和血管性痴呆（VaD）的发展有关。这项研究旨在评估血清和脑脊液（CSF）中PON1的变化，以证明其与AD或VaD相关。方法：对AD，VaD和CONTROLS患者的血清PON-芳基酯酶活性进行了测量，该人群分布在两个队列中：Ferrara队列（FC：n = 503，年龄= 74岁）和Amsterdam Dementia队列（ADC：n= 71，年龄= 65岁）。在最后一个队列中，还测量了CSF PON-芳基酯酶，CSFβ-淀粉样蛋白1-42，p-tau和t-tau以及成像生物标志物。结果：与对照组相比，FC的AD和VaD患者的血清PON-芳基酯酶水平明显降低，但这一结果是由年龄较大的受试者（> 71岁，p < 0.0001）驱动的。在较年轻的ADC中，血清和CSF观察到类似的下降（但不显着）趋势。有趣的是，AD组中每个APOA1的PON-芳基酯酶与t-tau相关（r = -0.485，p = 0.002）。结论：这些结果表明外周PON-芳基酯酶降低可能是老年AD / VaD患者的特征。此外，我们表明PON-芳基酯酶/ APOA1与AD患者的神经变性呈负相关，表明该复合参数对预后的有效性。