ICube Laboratory UMR 7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS team, University of Strasbourg and CNRS, Strasbourg, France.
Laboratory of Biochemistry and Molecular Biology, University Hospitals of Strasbourg, Strasbourg, France.
Neuropathol Appl Neurobiol. 2024 Feb;50(1):e12961. doi: 10.1111/nan.12961.
Chromogranin A (CgA) seems to be involved in the pathophysiology of different neurodegenerative pathologies such as Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB). CgA is present in the aggregates of amyloid plaques and in Lewy bodies but CgA also has a function in neuroinflammatory processes via microglia. Our objective was to determine if there is a difference in the CgA concentration in the cerebrospinal fluid (CSF) of AD and DLB patients and whether the CgA concentration can discriminate between the two diseases.
Using the previously described AlphaLewyMA cohort, we included 117 patients with a CSF CgA assay: 15 control subjects (CS group), 64 DLB patients, 17 AD patients and 21 patients with both AD and probable DLB criteria (AD/DLB group). CgA concentration was assessed using the MSD platform.
CSF CgA was increased in the AD and AD/DLB groups compared with the DLB group (p = 0.0006 between AD and DLB, p = 0.0013 between AD/DLB and DLB). No significant difference in CgA concentration was found between DLB and CS. ROC curve analysis showed an area under the curve of 0.791 between AD and DLB. CgA concentrations were correlated with t-Tau and P-Tau regardless of the pathology (for Tau: p = 0.022 for AD; p < 0.0001 for DLB; p = 0.004 for AD/DLB; for P-Tau: p = 0.032 for AD; p < 0.0001 for DLB; p = 0.0009 for AD/DLB). Aβ42 was positively correlated with CgA in the DLB group but not in the AD and AD/DLB groups (for DLB: p < 0.0001; for AD: p = 0.57; for AD/DLB: p = 0.58).
CSF CgA concentrations are increased in AD but not in DLB and correlate with P-Tau and Tau whatever the disease. These results suggest a link between tauopathy/neurodegeneration and CgA.
嗜铬粒蛋白 A(CgA)似乎参与了不同神经退行性病变的病理生理学过程,如阿尔茨海默病(AD)和路易体痴呆(DLB)。CgA 存在于淀粉样斑块的聚集物和路易体中,但 CgA 也通过小胶质细胞在神经炎症过程中发挥作用。我们的目的是确定 AD 和 DLB 患者脑脊液(CSF)中的 CgA 浓度是否存在差异,以及 CgA 浓度是否可以区分这两种疾病。
使用之前描述的 AlphaLewyMA 队列,我们纳入了 117 例进行 CSF CgA 检测的患者:15 名对照受试者(CS 组)、64 例 DLB 患者、17 例 AD 患者和 21 例同时符合 AD 和可能的 DLB 标准的患者(AD/DLB 组)。使用 MSD 平台评估 CgA 浓度。
与 DLB 组相比,AD 和 AD/DLB 组的 CSF CgA 升高(AD 与 DLB 之间 p=0.0006,AD/DLB 与 DLB 之间 p=0.0013)。DLB 与 CS 之间 CgA 浓度无显著差异。AD 与 DLB 之间的 ROC 曲线分析显示曲线下面积为 0.791。CgA 浓度与 Tau 无关,与病理状态有关(对于 Tau:AD 时 p=0.022;DLB 时 p<0.0001;AD/DLB 时 p=0.004;对于 P-Tau:AD 时 p=0.032;DLB 时 p<0.0001;AD/DLB 时 p=0.0009)。在 DLB 组中,Aβ42 与 CgA 呈正相关,但在 AD 和 AD/DLB 组中无相关性(DLB:p<0.0001;AD:p=0.57;AD/DLB:p=0.58)。
AD 患者的 CSF CgA 浓度升高,但 DLB 患者的 CgA 浓度不升高,与 P-Tau 和 Tau 均相关,无论疾病如何。这些结果表明 tau 病/神经退行性变与 CgA 之间存在联系。