title: Age-related intraneuronal accumulation of αII-spectrin breakdown product SBDP120 in the human cerebrum is enhanced in Alzheimer's disease.
abstract: Spectrins are a part of cytoskeletal platform that lines the intracellular side of plasma membrane, which can be proteolyzed by calcium-sensitive enzymes including calpains and caspases. Caspase-3 mediated αII-spectrin proteolysis results in the release of a 120kDa spectrin breakdown product (SBDP120), known to occur in conditions with cell death. In rodents, intraneuronal SBDP120 accumulation in the forebrain develops with age, which is enhanced in transgenic models of Alzheimer's disease (AD). The present study was set to explore age-related SBDP120 formation and its relevance to AD-type hallmark lesions in the human brains. SBDP120 immunoreactivity (IR) was detected in neuronal somata and dendrites in the cortex and hippocampal formation in postmortem brains from aged (n=10, mean age=84.2) and AD (n=10, mean age=84.8) subjects, but not mid-aged controls (n=10, mean age=58.2). The overall density of SBDP120 IR quantified in the temporal neocortex was increased in the aged and AD groups, more robust in the latter, relative to mid-aged control, while no regional, laminar or cellular association was found between SBDP120 accumulation and Aβ deposition or phosphorylated-tau aggregation. In cultured rat retinal ganglion cells (RGC-5), SBDP120 elevation occurred with caspase-3 activation following oxygen as well as serum deprivation, suggestive of SBDP120 formation in stressful conditions with and without apparent neuronal death. These results confirm an age-related intraneuronal SBDP120 accumulation in the human cerebrum that is enhanced in AD. This neuronal change appears to occur independent of amyloid deposition, tau pathology and overt neuronal death.
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan 410013, China; Department of Neurology, Central South University, The Third Affiliated Hospital of Xiangya School of Medicine, Changsha, Hunan 410013, China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Zhu
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan 410013, China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Xue
authors.affiliation: Department of Human Anatomy, Histology & Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100730, China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Qiu
authors.affiliation: Department of Molecular Biology, Central South University School of Basic Medical Science, Changsha, Hunan 410013, China.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Zeng
authors.affiliation: Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, China.
authors.forename: Jia-Pei
authors.initials: JP
authors.lastname: Dai
authors.affiliation: Department of Human Anatomy, Histology & Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100730, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan 410013, China.
authors.forename: Xue-Gang
authors.initials: XG
authors.lastname: Luo
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan 410013, China. Electronic address: yanxiaoxin@csu.edu.cn.
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Yan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; D010446:Peptide Fragments; C422208:Sptan1 protein, rat; D033921:Vesicular Transport Proteins; D016875:tau Proteins; D002154:Calpain; D020169:Caspases
keywords: Calcium stress; Cytoskeleton; Lipid bilayer; Neurodegeneration; Proteolysis