Characterization of a new set of monoclonal β-amyloid antibodies
Huan-Yu Che, Jia-Qi Ai, Chen Yang, Xiao-Lu Cai, Yan Wang, Juan Jiang, Qi-Lei Zhang, Tian Tu, Ewen Tu, Chong Che, Xiao-Xin Yan
β-Amyloid (Aβ) deposition is a commonly studied neuropathology in the human brain, occurring as compact and diffuse parenchymal plaques, cerebral amyloid angiopathy (CAA), and meningeal/subpial amyloidosis. Compact plaques associated with dystrophic neurites generally referred to as neuritic plaques, are a pathological hallmark of Alzheimer's disease (AD). We evaluated three recently developed monoclonal mouse antibodies against Aβ (A1, A2 and A3) using appropriate tissue samples and assay controls in the present study. In immunohistochemistry, antibodies A1, A2 and A3 displayed all forms of cerebral Aβ deposition in a range of dilutions in cryostat and paraffin sections. These labeled profiles appeared morphologically comparable to that visualized by two commercial Aβ antibody clones, 6E10 and D12B2. In immune-dot blotting assays, antibodies A1, A2 and A3 at highly diluted concentrations detected an increase of Aβ in neocortical lysates of AD samples compared to control. Moreover, these antibodies clearly labeled Aβ pathology in brain sections of three commonly used transgenic mouse models of AD, namely, APP/PS1 mice, 5XFAD mice, and 3XTg-AD mice. Taken together, these monoclonal mouse anti-Aβ antibodies can serve as new experimental tools for basic, translational, and diagnostic research into aging and AD-related cerebral Aβ neuropathology in both human and experimental animal brains.
Advances in human brain proteomics analysis of neurodegenerative diseases
Yashuang Chen, Xia Wang, Benhong Xu
Neurodegenerative diseases are characterized by progressive loss of neurons manifested as motor dysfunction and/or cognitive decline. Aberrant protein aggregation with altered physicochemical properties occurs in most neurodegenerative diseases. The pathophysiological mechanisms leading to the onset and progress of neurodegenerative diseases are still not fully understood. On the one hand, limited studies investigate neurodegenerative disease from human brain tissues. On the other, a comprehensive and efficient analysis method is needed to detect the signaling pathways evolved in neurodegenerative disease. Proteomics on human brains identifies key diagnostic biomarkers and treatment/therapeutic targets of neurodegenerative disorders. In recent years, several proteomics studies conducted on brain tissues from patients with neurodegenerative diseases have shown that changes in protein abundance or post-translational modification underly the disease pathogenesis. In this review, we summarize the major advances of human brain proteomics in the research on Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and Huntington’s disease as the most common neurodegenerative diseases. Finally, we proposed some perspective clues for future work.
Human Brain Banking as a Convergence Platform of Neuroscience and Neuropsychiatric Research
Fan Liu, Xiang-Sha Yin, Cong Cong, Yuanzhuo Wang, Chao Ma
Neuropsychiatric disorders affect hundreds of millions of people and their families worldwide. Many studies have used human postmortem brain samples to decipher the molecular framework of these diseases. These studies uncovered brain-specific genetic and epigenetic patterns using high-throughput sequencing techniques. Therefore, determining the best way to collect human postmortem brain samples, analysing such a large amount of sequencing data, and interpreting these results is critical to advancing the field of neuropsychiatric sciences. By collecting postmortem/biopsied neural tissues and information about the diseases and life of donors, human brain banks support the observation and research of human brain sciences. Furthermore, the construction of large-scale brain banks has promoted the exploration of human brain morphology and function, development and ageing, as well as the mechanism of many neuropsychiatric diseases, which progressively reveal the normal mechanism of human brain activities and lead the direction of the prevention and treatment of neurological diseases. This article introduces the significance of human brain tissue bank construction and the current situation of the human brain tissue bank worldwide, as well as an overview of neurology or neuroscience advanced by using human brain samples.
Brain structural and cerebrovascular changes and neurodegenerative pathologies are common and inadequately elucidated health problems in aging brains. Prospective population-based neuropathological studies play a unique role in neuropathological research. Brain weight decrease, arteriopathy, venular collagenosis, capillary loss, and accumulation of abnormal proteins are significant pathologies in the aging process. However, studies based on true population samples are scarce, and there is an ambiguity regarding the pathogenic proteinopathy between normal aging and neurodegenerative disease. Therefore, together population-based pathological studies offer an insight into the brain changes and diseases in the aging process, which could bring progress in the research for mechanisms and therapeutic interventions. Here, we reviewed findings from truly population-based pathological studies of brain aging and a range of neurodegenerative markers to better characterize brain pathological changes.
Leilei Wang, Haoran Wu, Shanshan Zhang, Dingxian He, Yi Chen , Jingxin Xue, Linya You, Qiong Liu, Wensheng Li
Microglia are tissue-resident macrophages of the central nervous system (CNS) that play crucial roles in development, homeostasis, and response to perturbation. Microglia react to the surrounding environment in a context-dependent manner. However, research on microglial heterogeneity is limited, given the lack of high-resolution and high-sensitivity methods. Recent studies have demonstrated the heterogeneity of microglia on a spatial-temporal scale, benefiting from the advancement of single-cell technologies. Here, we review the current knowledge about microglial diversity during physiological and pathological conditions in humans and mice.
Standardized Operational Protocol for the China Human Brain Bank Consortium
Wang Xue, Wu Juanli, Wang Naili, Zhang Di, Chen Zhen, Zhang Hanlin, Zhu Keqing, Bao Aimin, Zhang Jing, Shen Yi, Qian Xiaojing, Qiu Wenying
The study of post-mortem human brains is fundamental to the discovery and diagnosis of most neurological diseases and an in-depth understanding of brain structure, function and disorders. Human brain banks use a standardized protocol to collect, process, and store post-mortem human brains and related tissues, together with relevant clinical information, and to provide the tissue samples and data to foster neuroscience research. A Standardized Operational Protocol (SOP) that is approved by and can be abided by all of the human brain banks in the China Human Brain Bank Consortium is critical to developing brain research in China. The first SOP of human brain banking in China was published in 2017 following the foundation of the China Human Brain Bank Consortium. So far, 20 members from different regions in China have joined the consortium, forming a nationwide collaboration network of human brain banks. To provide brain tissue samples of good quality and consistency to meet the increasing demand for neuroscience research, a revised SOP was drafted by experts from the China Human Brain Bank Consortium. Significant improvements in this new version of SOP include strengthened ethical guidelines, recruitment of matching controls, and more brain regions to be sampled for neuropathological evaluation.