Neurodegeneration and astrogliosis in the entorhinal cortex in Alzheimer's disease: Stereological layer-specific assessment and proteomic analysis

被引:27
作者
Astillero-Lopez, Veronica [1 ]
Gonzalez-Rodriguez, Melania [1 ]
Villar-Conde, Sandra [1 ]
Flores-Cuadrado, Alicia [1 ]
Martinez-Marcos, Alino [1 ]
Ubeda-Banon, Isabel [1 ]
Saiz-Sanchez, Daniel [1 ]
机构
[1] Univ Castilla La Mancha, Neuroplast & Neurodegenerat Lab, CRIB, Ciudad Real Med Sch, Ciudad Real, Spain
关键词
Alzheimer's disease; entorhinal cortex; glia; neurons; proteomic; stereology; NEURONAL LOSS; PATHOLOGY; PROTEIN; NUMBER; BRAIN; CA1;
D O I
10.1002/alz.12580
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Introduction The entorhinal cortex is among the earliest areas involved in Alzheimer's disease. Volume reduction and neural loss in this area have been widely reported. Human entorhinal cortex atrophy is, in part, due to neural loss, but microglial and/or astroglial involvement in the different layers remains unclear. Additionally, -omic approaches in the human entorhinal cortex are scarce. Methods Herein, stereological layer-specific and proteomic analyses were carried out in the human brain. Results Neurodegeneration, microglial reduction, and astrogliosis have been demonstrated, and proteomic data have revealed relationships with up- (S100A6, PPP1R1B, BAG3, and PRDX6) and downregulated (GSK3B, SYN1, DLG4, and RAB3A) proteins. Namely, clusters of these proteins were related to synaptic, neuroinflammatory, and oxidative stress processes. Discussion Differential layer involvement among neural and glial populations determined by proteinopathies and identified proteins related to neurodegeneration and astrogliosis could explain how the cortical circuitry facilitates pathological spreading within the medial temporal lobe.
引用
收藏
页码:2468 / 2480
页数:13
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