Julius Center for Health Sciences and Primary Care (ELT, MK, WMMV, MIG), University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands; Amsterdam UMC, Location Vrije Universiteit (ELT), Department of General Practice, Amsterdam Public Health, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Julius Center for Health Sciences and Primary Care (ELT, MK, WMMV, MIG), University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
Am J Geriatr Psychiatry. 2024 Sep;32(9):1141-1153. doi: 10.1016/j.jagp.2024.03.004. Epub 2024 Mar 11.
Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aβ) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia.
A two-stage meta-analysis was performed on 2 clinic-based and 6 population-based cohorts (N = 7210) as part of the Netherlands Consortium of Dementia Cohorts. Plasma markers (Aβ42/40, p-tau181, NfL, and GFAP) were measured using Single Molecular Array (Simoa; Quanterix) assays. Depressive symptoms were measured with validated questionnaires. We estimated the cross-sectional association of each standardized plasma marker (determinants) with standardized depressive symptoms (outcome) using linear regressions, correcting for age, sex, education, and APOE ε4 allele presence, as well as subgrouping by sex and APOE ε4 allele. Effect estimates were entered into a random-effects meta-analysis.
Mean age of participants was 71 years. The prevalence of clinically relevant depressive symptoms ranged from 1% to 22%. None of the plasma markers were associated with depressive symptoms in the meta-analyses. However, NfL was associated with depressive symptoms only in APOE ε4 carriers (β 0.11; 95% CI: 0.05-0.17).
Late-life depressive symptoms did not show an association to plasma biomarkers of AD pathology. However, in APOE ε4 allele carriers, a more profound role of neurodegeneration was suggested with depressive symptoms.
抑郁症状与阿尔茨海默病（AD）的风险增加有关。最近出现了一些用于 AD 病理生理学的血浆生物标志物，如淀粉样蛋白-β（Aβ）和磷酸化 tau（p-tau），以及轴突损伤（神经丝轻链，NfL）和星形胶质细胞激活（胶质纤维酸性蛋白，GFAP）。假设抑郁症状可能沿着 AD 进程发生，我们研究了无痴呆个体中 AD 血浆生物标志物与抑郁症状之间的关联。
作为荷兰痴呆队列联盟的一部分，对 2 个基于临床的和 6 个基于人群的队列（N=7210）进行了两阶段荟萃分析。使用单分子阵列（Simoa；Quanterix）测定法测量了血浆标志物（Aβ42/40、p-tau181、NfL 和 GFAP）。使用经过验证的问卷测量抑郁症状。我们使用线性回归估计每个标准化血浆标志物（决定因素）与标准化抑郁症状（结果）的横断面关联，校正年龄、性别、教育程度和 APOE ε4 等位基因的存在，以及按性别和 APOE ε4 等位基因亚组化。将效应估计值纳入随机效应荟萃分析。
参与者的平均年龄为 71 岁。有临床意义的抑郁症状的患病率从 1%到 22%不等。在荟萃分析中，没有一种血浆标志物与抑郁症状相关。然而，NfL 仅与 APOE ε4 携带者的抑郁症状相关（β 0.11；95%CI：0.05-0.17）。
晚年抑郁症状与 AD 病理的血浆生物标志物无关联。然而，在 APOE ε4 等位基因携带者中，与抑郁症状相关的神经退行性变作用更为明显。
Zotero 插件