Association of increased cortical soluble Aβ42 levels with diffuse plaques after severe brain injury in humans
Association of increased cortical soluble Aβ42 levels with diffuse plaques after severe brain injury in humans
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DOI：
10.1001/archneur.64.4.541
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发表时间：
2007-04-01
影响因子：
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通讯作者：
Ikonomovic, Milos D.
中科院分区：
文献类型：
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作者：
DeKosky, Steven T.;Abrahamson, Eric E.;Ikonomovic, Milos D.
背景：外伤性脑损伤（TBI）是发生阿尔茨海默病的环境危险因素。这可能部分是由于与β -淀粉样蛋白（A β）斑块形成相关的变化，这种变化可能在受伤后数小时内发生，而与患者的年龄无关。除了作为沉积在斑块中的有毒原纤维的前体外，可溶性（非原纤维）A β肽被认为可以破坏突触功能，并与阿尔茨海默病的认知能力下降有关。TBI后可溶性A β水平的变化及其与A β斑块形成的关系尚不清楚。目的：量化脑外伤后脑组织可溶性A β肽及其前体蛋白水平与A β斑块形成的关系。设计：对手术切除的严重TBI患者的颞叶皮层组织进行生化分析，以氨基酸40 （A β(40)）或42 （A β(42)）结尾的可溶性A β肽和A β前体蛋白为终点，比较皮质A β斑块患者和非皮质A β斑块患者。患者：19名受试者在匹兹堡大学医学中心接受严重闭合性头部损伤的治疗。结果：严重TBI和皮质斑块患者可溶性A β水平较高（1-42），但A β水平不高（1-40）；半数为载脂蛋白E (APOE) ε 4等位基因携带者。A β水平最低的患者为1名无斑块的患者，该患者是唯一携带APOE 2等位基因的受试者。β -淀粉样蛋白前体蛋白水平在两组TBI中具有可比性。结论：脑外伤后可溶性A β(1-42)的选择性增加可能使脑损伤患者易患阿尔茨海默病。这可能受到APOE基因型的影响，它可能会增加晚年患阿尔茨海默病的风险。
Background: Traumatic brain injury (TBI) is an environmental risk factor for developing Alzheimer disease. This may be due, in part, to changes associated with beta-amyloid (A beta) plaque formation, which can occur within hours after injury, regardless of the patient's age. In addition to being precursors of toxic fibrils that deposit into plaques, soluble (nonfibrillar) A beta peptides are posited to disrupt synaptic function and are associated with cognitive decline in Alzheimer disease. Changes in soluble A beta levels and their relationship to A beta plaque formation following TBI are unknown.Objective: To quantify brain tissue levels of soluble A beta peptides and their precursor protein in relation to A beta plaque formation after TBI in humans.Design: Surgically resected temporal cortex tissue from patients with severe TBI was processed for biochemical assays of soluble A beta peptides with COOH-termini ending in amino acid 40 (A beta(40)) or 42 (A beta(42)) and A beta precursor protein to compare patients with cortical A beta plaques and those without.Patients: Nineteen subjects admitted to the University of Pittsburgh Medical Center for treatment of severe closed head injury.Results: Patients with severe TBI and cortical plaques had higher levels of soluble A beta(1-42) but not A beta(1-40); half of them were apolipoprotein E (APOE) epsilon 4 allele carriers. The lowest A beta levels were in 1 patient without plaques who was the only subject with an APOE epsilon 2 allele. beta-Amyloid precursor protein levels were comparable in the 2 TBI groups.Conclusions: Selective increases in soluble A beta(1-42) after TBI may predispose individuals with a brain injury to Alzheimer disease pathology. This may be influenced by the APOE genotype, and it may confer increased risk for developing Alzheimer disease later in life.