Ekblad Laura L, Visser Pieter Jelle, Tijms Betty M
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands; Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
Neurobiol Aging. 2021 Nov;107:42-52. doi: 10.1016/j.neurobiolaging.2021.07.003. Epub 2021 Jul 15.
Cortical atrophy is an early feature of Alzheimer´s disease (AD). The biological processes associated with variability in cortical thickness remain largely unknown. We studied 220 cerebrospinal fluid (CSF) proteins to evaluate biological pathways associated with cortical thickness in 34 brain regions in 79 cognitively normal older individuals with normal (>192 ng/L, n = 47), and abnormal (≤192 ng/L, n = 32) CSF beta-amyloid (Aβ). Interactions for Aβ status were tested. Panther GeneOntology and Cytoscape ClueGO analyses were used to evaluate biological processes associated with regional cortical thickness. 170 (77.3 %) proteins related with cortical thickness in at least 1 brain region across the total group, and 171 (77.7 %) proteins showed Aβ specific associations. Higher levels of proteins related to axonal and synaptic integrity, amyloid accumulation, and inflammation were associated with thinner cortex in lateral temporal regions, the rostral anterior cingulum, the lateral occipital cortex and the pars opercularis only in the abnormal Aβ group. Alterations in CSF proteomics are associated with a regional cortical atrophy in the earliest stages of AD.
皮质萎缩是阿尔茨海默病（AD）的早期特征。与皮质厚度变异性相关的生物学过程在很大程度上仍不清楚。我们研究了220种脑脊液（CSF）蛋白，以评估79名认知正常的老年人中34个脑区的皮质厚度相关生物学途径，这些老年人的脑脊液β-淀粉样蛋白（Aβ）水平正常（>192 ng/L，n = 47）或异常（≤192 ng/L，n = 32）。测试了Aβ状态的相互作用。使用Panther基因本体论和Cytoscape ClueGO分析来评估与区域皮质厚度相关的生物学过程。在整个组中，170种（77.3%）蛋白与至少1个脑区的皮质厚度相关，171种（77.7%）蛋白显示出Aβ特异性关联。仅在异常Aβ组中，与轴突和突触完整性、淀粉样蛋白积累及炎症相关的蛋白水平升高与颞叶外侧区、喙前扣带回、枕叶外侧皮质和岛盖部的皮质变薄有关。脑脊液蛋白质组学的改变与AD最早阶段的区域皮质萎缩有关。
