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_1-42 (Aβ₄₂). Interactions for Aβ₄₂ 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 Aβ₄₂ 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 Aβ₄₂ 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。与皮质厚度变化相关的生物学过程在很大程度上仍然未知。我们研究了 220 种脑脊液 (CSF) 蛋白，以评估与正常 (>192 ng/L, n = 47) 和异常 (≤192 ng/L, n = 32) CSF β-淀粉样蛋白_1-42 (Aβ ₄₂ )。Aβ _{42的相互作用}状态进行了测试。Panther GeneOntology 和 Cytoscape ClueGO 分析用于评估与区域皮质厚度相关的生物过程。170 种 (77.3 %) 蛋白质与整个组中至少 1 个脑区的皮质厚度相关，171 种 (77.7 %) 蛋白质显示出 Aβ ₄₂特异性关联。_{仅在异常 Aβ 42}组中，与轴突和突触完整性、淀粉样蛋白积累和炎症相关的较高水平的蛋白质与外侧颞区、前扣带回、枕外侧皮质和枕部皮质较薄有关。脑脊液蛋白质组学的改变与 AD 早期的区域性皮质萎缩有关。