揭示非痴呆个体脑脊髓液中淀粉样蛋白病理阳性的潜在生物标志物。

Unveiling Potential Biomarkers in Cerebrospinal Fluid for Amyloid Pathological Positivity in Non-Demented Individuals.

机构信息

Prof. Xi Zhang, Department of Neurology, The Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China, School of Medicine, Nankai University, Tianjin, 300071, China, E-mail:

出版信息

J Prev Alzheimers Dis. 2024;11(6):1759-1766. doi: 10.14283/jpad.2024.129.

DOI:10.14283/jpad.2024.129

PMID:39559887

Abstract

BACKGROUND

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation and neurofibrillary tangles. The recent approval of anti-amyloid therapeutic medications highlights the crucial need for early detection of Aβ pathological abnormalities in individuals without dementia to facilitate timely intervention and treatment.

OBJECTIVE

The primary aim of this study was to identify cerebrospinal fluid (CSF) biomarkers strongly associated with Aβ pathological positivity in a non-demented cohort and evaluate their clinical values.

METHODS

A comprehensive analysis was conducted on 51 CSF proteins (excluding Aβ42, pTau, and Tau) obtained from 474 non-demented participants sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. By utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression, we identified potential proteins indicative of Aβ pathological positivity and evaluated their performance in tracking longitudinal pathological progression.

RESULTS

Our LASSO analysis unveiled three candidates: apolipoprotein E (APOE), chitinase-3-like protein 1 (CHI3L1), and SPARC-related modular calcium-binding protein 1 (SMOC1). While SMOC1 did not correlate with Aβ42-related cognitive alterations, it displayed better abilities in discriminating both CSF-Aβ positivity and Aβ-positron emission tomography (PET) positivity than the other two candidates. It could precisely predict longitudinal Aβ-PET status conversion. Notably, SMOC1 was the only protein showing associations with longitudinal Aβ-PET trajectory and enhancing the diagnostic accuracy of Aβ42. The assessment of combined Aβ42 and SMOC1 yielded valuable clinical insights.

CONCLUSION

Our findings elucidated SMOC1 as a potential biomarker for detecting Aβ abnormalities. Aβ42 combining SMOC1 offered critical implications in AD pathological diagnosis and management.

摘要

背景

阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是淀粉样β（Aβ）斑块积累和神经原纤维缠结。最近批准的抗淀粉样蛋白治疗药物突出强调了在没有痴呆的个体中早期检测 Aβ 病理异常的重要性，以便及时进行干预和治疗。

目的

本研究的主要目的是在非痴呆队列中确定与 Aβ 病理阳性密切相关的脑脊液（CSF）生物标志物，并评估其临床价值。

方法

对来自阿尔茨海默病神经影像学倡议（ADNI）数据库的 474 名非痴呆参与者的 51 种 CSF 蛋白（不包括 Aβ42、pTau 和 Tau）进行了全面分析。我们利用最小绝对收缩和选择算子（LASSO）回归确定了潜在的 Aβ 病理阳性标志物，并评估了它们在跟踪纵向病理进展方面的性能。

结果

我们的 LASSO 分析揭示了三个候选物：载脂蛋白 E（APOE）、几丁质酶 3 样蛋白 1（CHI3L1）和富含丝氨酸/精氨酸的酸性分泌糖蛋白 1（SPARC-related modular calcium-binding protein 1，SMOC1）。虽然 SMOC1 与 Aβ42 相关的认知改变无关，但它在区分 CSF-Aβ 阳性和 Aβ-正电子发射断层扫描（PET）阳性方面的能力优于其他两个候选物。它可以精确预测纵向 Aβ-PET 状态转换。值得注意的是，SMOC1 是唯一与纵向 Aβ-PET 轨迹相关并提高 Aβ42 诊断准确性的蛋白。联合评估 Aβ42 和 SMOC1 具有重要的临床意义。