Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Department of Biomedicine, University of Barcelona, Barcelona, Spain.
Neurobiol Aging. 2020 Sep;93:1-15. doi: 10.1016/j.neurobiolaging.2020.04.002. Epub 2020 Apr 15.
Brain changes occurring in aging can be indexed by biomarkers. We used cluster analysis to identify subgroups of cognitively unimpaired individuals (n = 99, 64-93 years) with different profiles of the cerebrospinal fluid biomarkers beta amyloid 1-42 (Aβ42), phosphorylated tau (P-tau), total tau, chitinase-3-like protein 1 (YKL-40), fatty acid binding protein 3 (FABP3), and neurofilament light (NFL). Hippocampal volume and memory were assessed across multiple follow-up examinations covering up to 6.8 years. Clustering revealed one group (39%) with more pathological concentrations of all biomarkers, which could further be divided into one group (20%) characterized by tauopathy and high FABP3 and one (19%) by brain β-amyloidosis, high NFL, and slightly higher YKL-40. The clustering approach clearly outperformed classification based on Aβ42 and P-tau alone in prediction of memory decline, with the individuals with most tauopathy and FABP3 showing more memory decline, but not more hippocampal volume change. The results demonstrate that older adults can be classified based on biomarkers beyond amyloid and tau, with improved prediction of memory decline.
大脑老化过程中的变化可以通过生物标志物进行指标检测。我们使用聚类分析来识别认知功能正常的个体（n=99，年龄在 64-93 岁）亚组，这些个体的脑脊液生物标志物β淀粉样蛋白 1-42（Aβ42）、磷酸化 tau（P-tau）、总 tau、几丁质酶 3 样蛋白 1（YKL-40）、脂肪酸结合蛋白 3（FABP3）和神经丝轻链（NFL）水平存在不同的特征。通过多次随访检查评估了海马体积和记忆，随访时间最长可达 6.8 年。聚类分析显示，有 39%的个体具有所有生物标志物浓度更高的病理特征，这些个体可以进一步分为两组，一组（20%）表现为 tau 病和 FABP3 水平高，另一组（19%）则表现为脑β-淀粉样蛋白沉积、NFL 水平高和 YKL-40 水平略高。与单独基于 Aβ42 和 P-tau 的分类方法相比，聚类方法在预测记忆衰退方面表现更优，tau 病和 FABP3 水平较高的个体记忆衰退更为明显，但海马体积变化不明显。结果表明，除了淀粉样蛋白和 tau 之外，还可以基于其他生物标志物对老年人进行分类，从而更好地预测记忆衰退。
