Rabl Miriam, Clark Christopher, Dayon Loïc, Popp Julius
Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Psychiatric University Hospital, Zurich, Switzerland.
Nestlé Institute of Food Safety & Analytical Sciences, Nestlé Research, Lausanne, Switzerland.
J Neurol Neurosurg Psychiatry. 2025 Mar 24;96(4):370-382. doi: 10.1136/jnnp-2024-333819.
Neuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer's disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This study aimed to identify plasma proteins that may serve as biomarkers for NPS and NPS-related clinical disease progression.
A panel of 190 plasma proteins was quantified using Luminex xMAP in the Alzheimer's Disease Neuroimaging Initiative cohort. NPS and cognitive performance were assessed at baseline and after 1 and 2 years. Logistic regression, receiver operating characteristic analysis and cross-validation were used to address the relations of interest.
A total of 507 participants with mild cognitive impairment (n=396) or mild AD dementia (n=111) were considered. Selected plasma proteins improved the prediction of NPS (area under the curve (AUC) from 0.61 to 0.76, p<0.001) and future NPS (AUC from 0.63 to 0.80, p<0.001) when added to a reference model. Distinct protein panels were identified for single symptoms. Among the selected proteins, ANGT, CCL1 and IL3 were associated with NPS at all three time points while CCL1, serum glutamic oxaloacetic transaminase and complement factor H were also associated with cognitive decline. The associations were independent of the presence of cerebral AD pathology as assessed using cerebrospinal fluid biomarkers.
Plasma proteins are associated with NPS and improve prediction of future NPS.
神经精神症状（NPS）在患有认知障碍和阿尔茨海默病（AD）的老年人中很常见。目前尚无检测相关病理或预测NPS临床进展的生物标志物。本研究旨在确定可能作为NPS及NPS相关临床疾病进展生物标志物的血浆蛋白。
在阿尔茨海默病神经影像学倡议队列中，使用Luminex xMAP技术对一组190种血浆蛋白进行定量分析。在基线以及1年和2年后评估NPS和认知表现。采用逻辑回归、受试者工作特征分析和交叉验证来处理相关关系。
共纳入507名轻度认知障碍患者（n = 396）或轻度AD痴呆患者（n = 111）。当将选定的血浆蛋白添加到参考模型中时，可改善对NPS的预测（曲线下面积（AUC）从0.61提高到0.76，p < 0.001）以及对未来NPS的预测（AUC从0.63提高到0.80，p < 0.001）。针对单一症状确定了不同的蛋白组。在选定的蛋白中，血管生成素（ANGT）、趋化因子配体1（CCL1）和白细胞介素3（IL3）在所有三个时间点均与NPS相关，而CCL1、血清谷草转氨酶和补体因子H也与认知衰退相关。这些关联独立于使用脑脊液生物标志物评估的脑内AD病理的存在情况。
血浆蛋白与NPS相关，并可改善对未来NPS的预测。
