BACE1 elevation in transgenic mouse model of Alzheimer’s disease is associated with synaptic/axonal pathology and amyloidogenesis
作者单位：Department of Pathology and NeuroscienceThe Johns Hopkins University School of MedicineBaltimoreMaryland 21205 Department of AnatomySouthern Illinois University School of MedicineCarbondaleIllinois 62901
会议名称：《中国神经科学学会第四次会员代表大会暨第八届全国学术会议》
会议日期：2009年
学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学]
关 键 词：aging dementia secretase amyloid plaques dystrophic neurite axonopathy
摘 要：正How amyloid plaques develop in the brain represents the central yet unsettled question in Alzheimer’s disease （AD） *** hypothesis postulate thatβ-amyloid peptide（Ap） deposits are either the cause or the consequence of vascular,glial and neuronal *** proteins includingβ-amyloid precursor protein （APP）,and its cleavage enzymes,β-secretase（BACE1） andβ-secretase,appear to be expressed largely in neurons, supporting a notion that Aβdeposits originate from neuronal *** depositions may exist either as neuritic or diffuse forms,with the former being associated with dystrophic *** phenomenon appears as if dystrophic neurites and Aβdeposits do not necessarily precede one to *** and axonal terminals have been considered the origin of extracellular Aβ***,anatomic evidence for early synaptic/axonal alterations preceding or coevolving with plaque onset and evolution is yet to be *** study determined the localization of elevated BACE1 expression relative to Aβaccumulation and synaptic/neuritic alterations in transgenic（Tg） mice harboring familial AD（FAD） mutations（5XFAD,2XFAD,3xTg-AD mice）.BACE1 immunoreactivity（ir） coexisted with compact plaques in the cortex and hippocampus of all transgenics,occurring in dystrophic axonal neurites of various neuronal origins（GABAergic,glutamatergic,cholinergic or catecholaminergic）.Compact plaques within the cortical grey matter appeared to mainly derive from BACE/Aβlabeled presynaptic terminals surrounding pyramidal neurons with cytoplasmic Aβ-ir,and some of these terminals undergone sprouting to become overt dystrophic *** plaques appeared to evolve into cored plaques as extracellular Aβaccumulated within/around the growing mass of sprouting dystrophic *** old 3xTg-AD mice,the superficial cortical layers largely expressed diffuse plaques. Development of these diffuse plaques with age was associated with increased BACE