阿尔茨海默病尸检脑组织中的线粒体功能与 Aβ
Mitochondrial function and Aβ in Alzheimer's disease postmortem brain.
机构信息
University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA.
出版信息
Neurobiol Dis. 2022 Sep;171:105781. doi: 10.1016/j.nbd.2022.105781. Epub 2022 Jun 3.
INTRODUCTION
Mitochondrial dysfunction is observed in Alzheimer's disease (AD). However, the relationship between functional mitochondrial deficits and AD pathologies is not well established in human subjects.
METHODS
Post-mortem human brain tissue from 11 non-demented (ND) and 12 AD subjects was used to examine mitochondrial electron transport chain (ETC) function. Data were analyzed by neuropathology diagnosis and Apolipoprotein E (APOE) genotype. Relationships between AD pathology and mitochondrial function were determined.
RESULTS
AD subjects had reductions in brain cytochrome oxidase (COX) function and complex II Vmax. APOE ε4 carriers had COX, complex II and III deficits. AD subjects had reduced expression of Complex I-III ETC proteins, no changes were observed in APOE ε4 carriers. No correlation between p-Tau Thr 181 and mitochondrial outcomes was observed, although brains from non-demented subjects demonstrated positive correlations between Aβ concentration and COX Vmax.
DISCUSSION
These data support a dysregulated relationship between brain mitochondrial function and Aβ pathology in AD.
简介
在阿尔茨海默病（AD）中观察到线粒体功能障碍。然而，在人类受试者中，功能性线粒体缺陷与 AD 病理之间的关系尚未得到很好的建立。
方法
使用 11 名非痴呆（ND）和 12 名 AD 受试者的死后人脑组织来检查线粒体电子传递链（ETC）功能。数据分析基于神经病理学诊断和载脂蛋白 E（APOE）基因型。确定 AD 病理学与线粒体功能之间的关系。
结果
AD 受试者的脑细胞色素氧化酶（COX）功能和复合物 II Vmax 降低。APOE ε4 携带者有 COX、复合物 II 和 III 缺陷。AD 受试者的复合物 I-III ETC 蛋白表达减少，而 APOE ε4 携带者没有观察到变化。p-Tau Thr 181 与线粒体结果之间没有相关性，尽管来自非痴呆受试者的大脑显示 Aβ 浓度与 COX Vmax 之间存在正相关。
讨论
这些数据支持 AD 中脑线粒体功能与 Aβ 病理学之间失调的关系。
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