Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Bayer Pharma AG, Berlin, Germany.
J Alzheimers Dis. 2021;80(4):1723-1737. doi: 10.3233/JAD-201344.
Emerging evidence indicates a central role of gliosis in Alzheimer's disease (AD) pathophysiology. However, the regional distribution and interaction of astrogliosis and microgliosis in association with amyloid-β (Aβ) still remain uncertain.
Here we studied the pathological profiles in autopsy AD brain by using specific imaging tracers.
Autopsy brain tissues of AD (n = 15, age 70.4±8.5 years) and control cases (n = 12, age 76.6±10.9) were examined with homogenate binding assays, autoradiography for Aβ plaques (3H-florbetaben/3H-PIB), astrogliosis (3H-L-deprenyl), and microgliosis (3H-PK11195/3H-FEMPA), as well as immunoassays.
In vitro saturation analysis revealed high-affinity binding sites of 3H-florbetaben, 3H-L-deprenyl, and 3H-PK11195/3H-FEMPA in the frontal cortex of AD cases. In vitro3H-florbetaben binding increased across cortical and subcortical regions of AD compared to control with the highest binding in the frontal and parietal cortices. The in vitro3H-L-deprenyl binding showed highest binding in the hippocampus (dentate gyrus) followed by cortical and subcortical regions of AD while the GFAP expression was upregulated only in the hippocampus compared to control. The in vitro3H-PK11195 binding was solely increased in the parietal cortex and the hippocampus of AD compared to control. The 3H-florbetaben binding positively correlated with the 3H-L-deprenyl binding in the hippocampus and parietal cortex of AD and controls. Similarly, a positive correlation was observed between 3H-florbetaben binding and GFAP expression in hippocampus of AD and control.
The use of multi-imaging tracers revealed different regional pattern of changes in autopsy AD brain with respect to amyloid plaque pathology versus astrogliosis and microgliosis.
新出现的证据表明神经胶质细胞增生在阿尔茨海默病（AD）的病理生理学中起着核心作用。然而，星形胶质细胞增生和小胶质细胞增生与淀粉样蛋白-β（Aβ）的区域分布和相互作用仍不确定。
本研究使用特定的成像示踪剂研究尸检 AD 脑的病理特征。
使用匀浆结合分析、放射性配体结合分析（3H-氟比汀/3H-PIB 用于检测 Aβ斑块、3H-L-丙炔苯丙胺用于检测星形胶质细胞增生、3H-PK11195/3H-FEMPA 用于检测小胶质细胞增生）和免疫测定法，对 AD（n=15，年龄 70.4±8.5 岁）和对照组（n=12，年龄 76.6±10.9 岁）的尸检脑组织进行检查。
体外饱和分析显示，AD 病例额皮质 3H-氟比汀、3H-L-丙炔苯丙胺和 3H-PK11195/3H-FEMPA 具有高亲和力结合位点。与对照组相比，AD 患者额皮质和皮质下区域的 3H-氟比汀结合增加，额皮质和顶皮质的结合最高。体外 3H-L-丙炔苯丙胺结合显示，AD 患者的海马（齿状回）结合最高，其次是皮质和皮质下区域，而 GFAP 表达仅在海马与对照组相比上调。体外 3H-PK11195 结合仅在 AD 患者的顶叶皮质和海马中增加，与对照组相比。AD 患者和对照组的 3H-氟比汀结合与 3H-L-丙炔苯丙胺结合在海马和顶叶皮质中呈正相关。同样，AD 和对照组海马中的 3H-氟比汀结合与 GFAP 表达呈正相关。
使用多成像示踪剂显示了尸检 AD 脑在淀粉样斑块病理学与星形胶质细胞增生和小胶质细胞增生方面的不同区域模式变化。
