阿尔茨海默病中异常的TDP-43免疫反应性改变临床病理和放射学表型。
Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype.
作者信息
Josephs K A, Whitwell J L, Knopman D S, Hu W T, Stroh D A, Baker M, Rademakers R, Boeve B F, Parisi J E, Smith G E, Ivnik R J, Petersen R C, Jack C R, Dickson D W
机构信息
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
出版信息
Neurology. 2008 May 6;70(19 Pt 2):1850-7. doi: 10.1212/01.wnl.0000304041.09418.b1. Epub 2008 Apr 9.
BACKGROUND
TAR DNA-binding protein 43 (TDP-43) is one of the major disease proteins in frontotemporal lobar degeneration with ubiquitin immunoreactivity. Approximately one-fourth of subjects with pathologically confirmed Alzheimer disease (AD) have abnormal TDP-43 (abTDP-43) immunoreactivity. The aim of this study was to determine whether subjects with pathologically confirmed AD and abTDP-43 immunoreactivity have distinct clinical, neuropsychological, imaging, or pathologic features compared with subjects with AD without abTDP-43 immunoreactivity.
METHODS
Eighty-four subjects were identified who had a pathologic diagnosis of AD, neuropsychometric testing, and volumetric MRI. Immunohistochemistry for TDP-43 was performed on sections of hippocampus and medial temporal lobe, and positive cases were classified into one of three types. Neuropsychometric data were collated and compared in subjects with and without abTDP-43 immunoreactivity. Voxel-based morphometry was used to assess patterns of gray matter atrophy in subjects with and without abTDP-43 immunoreactivity compared with age- and sex-matched controls.
RESULTS
Twenty-nine (34%) of the 84 AD subjects had abTDP-43 immunoreactivity. Those with abTDP-43 immunoreactivity were older at onset and death and performed worse on the Clinical Dementia Rating scale, Mini-Mental State Examination, and Boston Naming Test than subjects without abTDP-43 immunoreactivity. Subjects with and without abTDP-43 immunoreactivity had medial temporal and temporoparietal gray matter loss compared with controls; however, those with abTDP-43 immunoreactivity showed greater hippocampal atrophy. Multivariate logistic regression adjusting for age at death demonstrated that hippocampal sclerosis was the only pathologic predictor of abTDP-43 immunoreactivity.
CONCLUSIONS
The presence of abnormal TDP-43 immunoreactivity is associated with a modified Alzheimer disease clinicopathologic and radiologic phenotype.
背景
TAR DNA结合蛋白43（TDP - 43）是具有泛素免疫反应性的额颞叶变性中的主要疾病蛋白之一。约四分之一经病理证实的阿尔茨海默病（AD）患者具有异常的TDP - 43（abTDP - 43）免疫反应性。本研究的目的是确定与无abTDP - 43免疫反应性的AD患者相比，经病理证实的AD且具有abTDP - 43免疫反应性的患者是否具有不同的临床、神经心理学、影像学或病理学特征。
方法
确定了84名经病理诊断为AD、进行了神经心理测试和容积MRI的受试者。对海马体和内侧颞叶切片进行TDP - 43免疫组织化学检测，阳性病例分为三种类型之一。整理并比较有和无abTDP - 43免疫反应性的受试者的神经心理数据。基于体素的形态学测量用于评估有和无abTDP - 43免疫反应性的受试者与年龄和性别匹配的对照组相比的灰质萎缩模式。
结果
84名AD受试者中有29名（34%）具有abTDP - 43免疫反应性。与无abTDP - 43免疫反应性的受试者相比，有abTDP - 43免疫反应性的受试者发病和死亡时年龄更大，在临床痴呆评定量表、简易精神状态检查和波士顿命名测试中的表现更差。与对照组相比，有和无abTDP - 43免疫反应性的受试者均有内侧颞叶和颞顶叶灰质丢失；然而，有abTDP - 43免疫反应性的受试者海马萎缩更严重。对死亡年龄进行校正的多变量逻辑回归表明，海马硬化是abTDP - 43免疫反应性的唯一病理预测指标。
结论
异常TDP - 43免疫反应性的存在与改良的阿尔茨海默病临床病理和放射学表型相关。
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