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

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Neuroscience Bulletin 2022年第10期38卷 1125-1138页

作者： Fan Liu Jianru Sun Xue Wang Sixuan Jin Fengrun Sun Tao Wang Bo Yuan Wenying Qiu Chao Ma National human brain bank for Development and Function School of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesBeijing 100005China Department of human Anatomy Histology and EmbryologyNeuroscience CenterSchool of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesBeijing 100005China Chinese Institute for brain Research Beijing 102206China

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 *** has been found that there are different types of Aβplaque(diffuse and focal types)in the postmortem human *** 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 *** results indicated that focal plaques,but not diffuse plaques,significantly increased with age in the human *** 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 *** 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

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Correlations Between Single Nucleotide Polymorphisms,Cognitive Dysfunction,and Postmortem brain Pathology in Alzheimer's Disease Among Han Chinese

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Neuroscience Bulletin 2019年第2期35卷 193-204页

作者： Qian Yang Kang Chen Hanlin Zhang Wanying Zhang Changlin Gong Qing Zhang Pan Liu Tianyi Sun Yuanyuan Xu Xiaojing Qian Wenying Qiu Chao Ma Institute of Basic Medical Sciences Department of Human AnatomyHistology and EmbryologyNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical College Joint Laboratory of Anesthesia and Pain Peking Union Medical College Eight-Year MD Program Peking Union Medical College Johns Hopkins Bloomberg School of Public Health National Experimental Teaching Demonstration Center of Basic Medicine Peking Union Medical College

In this study, the distribution of five Alzheimer's disease(AD)-related single nucleotide polymorphisms(SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs,clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College(CAMS/PUMC) human brain *** ?4(OR = 4.482, P = 0.004), the RS2305421 GG genotype(adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype(adjusted OR = 2.375,P = 0.028) were associated with a higher score on the ABC(Ab plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD,the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.

关键词： human brain bank Alzheimer's disease APOEε4 ADAM10 SLC24A4

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