Focal-type,but not Diffuse-type,Amyloid Beta Plaques are Correlated with Alzheimer’s Neuropathology,Cognitive Dysfunction,and Neuroinflammation in the Human Hippocampus  

作　　者：Fan Liu Jianru Sun Xue Wang Sixuan Jin Fengrun Sun Tao Wang Bo Yuan Wenying Qiu Chao Ma 

机构地区：[1]National Human Brain Bank for Development and Function,School of Basic Medicine Peking Union Medical College,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,Beijing 100005,China [2]Department of Human Anatomy,Histology and Embryology,Neuroscience Center,School of Basic Medicine Peking Union Medical College,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,Beijing 100005,China [3]Chinese Institute for Brain Research,Beijing 102206,China

出　　处：《Neuroscience Bulletin》2022年第10期1125-1138,共14页神经科学通报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(81771205 and 81801114);the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-025);Science Innovation 2030–Brain Science and BrainInspired Intelligence Technology Major Project(2021ZD0201100 and 2021ZD0201101).We thank Dr.Xiaojin Qian and Dr.Yongmei Chen(Department of Anatomy,Histology and Embryology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences)for technical assistance in immunohistochemistry.

摘　　要：Amyloid beta(Aβ)plaques are one of the hallmarks of Alzheimer’s disease(AD).However,currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans.It has been found that there are different types of Aβplaque(diffuse and focal types)in the postmortem human brain.In this study,we aimed to investigate the correlations among different types of Aβplaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China.The results indicated that focal plaques,but not diffuse plaques,significantly increased with age in the human hippocampus.We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes(measured by the“ABC”scoring system)and cognitive decline(measured by the Everyday Cognitive Insider Questionnaire).Furthermore,most of the focal plaques were co-localized with neuritic plaques(identified by Bielschowsky silver staining)and accompanied by microglial and other inflammatory cells.Our findings suggest the potential of using focal-type but not general Aβplaques as biomarkers for the neuropathological evaluation of AD.

关 键 词：Focal Aβ plaques ECog score ABC score Alzheimer’s disease NEUROINFLAMMATION Clinicopathological correlation Human brain bank 

分 类 号：R-332[医药卫生] R749.16