Focal-type, but not Diffuse-type, Amyloid Beta Plaques are Correlated with Alzheimer's Neuropathology, Cognitive Dysfunction, and Neuroinflammation in the Human Hippocampus
Fan Liu1,2 · Jianru Sun2 · Xue Wang1,2 · Sixuan Jin2 · Fengrun Sun2 · Tao Wang2 · Bo Yuan2 · Wenying Qiu1,2 · Chao Ma1,2,3 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
Abstract
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 Aβ plaque (diffuse and focal types) in the postmortem human brain. In this study, we aimed to investigate the correlations among different types of Aβ plaque 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 Aβ plaques as biomarkers for the neuropathological evaluation of AD.
Keywords
Focal Aβ plaques · ECog score · ABC score · Alzheimer's disease · Neuroinfammation · Clinicopathological correlation · Human brain bank
