School of Clinical Medicine, Shandong Second Medical University (formerly Weifang Medical University), Weifang 261000, Shandong, China.
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Curr Alzheimer Res. 2024;21(3):201-213. doi: 10.2174/0115672050314397240708060314.
The study aims to determine whether multimorbidity status is associated with cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders.
A total of 827 patients were enrolled from the Parkinson's Progression Markers Initiative (PPMI) database, including 638 patients with early-stage Parkinson's disease (PD) and 189 healthy controls (HCs). Multimorbidity status was evaluated based on the count of long-term conditions (LTCs) and the multimorbidity pattern. Using linear regression models, cross-sectional and longitudinal analyses were conducted to assess the associations of multimorbidity status with CSF biomarkers for neurodegenerative disorders, including α-synuclein (αSyn), amyloid-β (Aβ), total tau (t-tau), phosphorylated tau (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL).
At baseline, the CSF t-tau (p = 0.010), p-tau (p = 0.034), and NfL (p = 0.049) levels showed significant differences across the three categories of LTC counts. In the longitudinal analysis, the presence of LTCs was associated with lower Aβ (β < -0.001, p = 0.020), and higher t-tau (β = 0.007, p = 0.026), GFAP (β = 0.013, p = 0.022) and NfL (β = 0.020, p = 0.012); Participants with tumor/musculoskeletal/mental disorders showed higher CSF levels of t-tau (β = 0.016, p = 0.011) and p-tau (β = 0.032, p = 0.044) than those without multimorbidity.
Multimorbidity, especially severe multimorbidity and the pattern of mental/musculoskeletal/ tumor disorders, was associated with CSF biomarkers for neurodegenerative disorders in early-stage PD patients, suggesting that multimorbidity might play a crucial role in aggravating neuronal damage in neurodegenerative diseases.
本研究旨在确定多病症状态是否与神经退行性疾病的脑脊液（CSF）生物标志物有关。
本研究共纳入了来自帕金森病进展标志物倡议（PPMI）数据库的 827 名患者，包括 638 名早期帕金森病（PD）患者和 189 名健康对照（HC）。根据长期疾病（LTC）的数量和多病症模式评估多病症状态。使用线性回归模型，进行横断面和纵向分析，以评估多病症状态与神经退行性疾病的 CSF 生物标志物之间的关联，包括α-突触核蛋白（αSyn）、淀粉样β（Aβ）、总tau（t-tau）、磷酸化tau（p-tau）、神经胶质纤维酸性蛋白（GFAP）和神经丝轻链蛋白（NfL）。
在基线时，CSF t-tau（p = 0.010）、p-tau（p = 0.034）和 NfL（p = 0.049）水平在 LTC 计数的三个类别之间存在显著差异。在纵向分析中，存在 LTC 与 Aβ降低相关（β < -0.001，p = 0.020），与 t-tau升高相关（β = 0.007，p = 0.026）、GFAP（β = 0.013，p = 0.022）和 NfL（β = 0.020，p = 0.012）；与肿瘤/肌肉骨骼/精神障碍相关的患者具有更高的 CSF t-tau（β = 0.016，p = 0.011）和 p-tau（β = 0.032，p = 0.044）水平。
多病症，特别是严重的多病症和精神/肌肉骨骼/肿瘤障碍模式，与早期 PD 患者的神经退行性疾病 CSF 生物标志物有关，表明多病症可能在加重神经退行性疾病中的神经元损伤方面发挥关键作用。
