路易体病中 tau 病理学的认知和病理影响。
Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders.
机构信息
Department of Neurology, Perelman School of Medicine at the University of Pennsylvania.
Digital Neuropathology Laboratory, Perelman School of Medicine at the University of Pennsylvania.
出版信息
Ann Neurol. 2019 Feb;85(2):259-271. doi: 10.1002/ana.25392. Epub 2019 Jan 7.
OBJECTIVE
To use digital histology in a large autopsy cohort of Lewy body disorder (LBD) patients with dementia to test the hypotheses that co-occurring Alzheimer disease (AD) pathology impacts the anatomic distribution of α-synuclein (SYN) pathology and that co-occurring neocortical tau pathology in LBDs associates with worse cognitive performance and occurs in a pattern differing from AD.
METHODS
Fifty-five autopsy-confirmed LBD (Parkinson disease with dementia, n = 36; dementia with Lewy bodies, n = 19) patients and 25 AD patients were studied. LBD patients were categorized as having moderate/severe AD copathology (SYN + AD = 20) or little/no AD copathology (SYN-AD = 35). Digital measures of tau, β-amyloid (Aβ), and SYN histopathology in neocortical and subcortical/limbic regions were compared between groups and related to antemortem cognitive testing.
RESULTS
SYN burden was higher in SYN + AD than SYN-AD in each neocortical region (F = 5.6-6.0, p < 0.02) but was equivalent in entorhinal cortex and putamen (F = 0.7-1.7, p > 0.2). SYN + AD performed worse than SYN-AD on a temporal lobe-mediated naming task (t = 2.1, p = 0.04). Antemortem cognitive test scores inversely correlated with tau burden (r = -0.39 to -0.68, p < 0.05). AD had higher tau than SYN + AD in all regions (F = 12.8-97.2, p < 0.001); however, SYN + AD had a greater proportion of tau in the temporal neocortex than AD (t = 2.0, p < 0.05), whereas AD had a greater proportion of tau in the frontal neocortex than SYN + AD (t = 3.3, p < 0.002). SYN + AD had similar severity and distribution of neocortical Aβ compared to AD (F = 1.6-2.0, p > 0.1).
INTERPRETATION
LBD patients with AD copathology harbor greater neocortical SYN pathology. Regional tau pathology relates to cognitive performance in LBD dementia, and its distribution may diverge from pure AD. Tau copathology contributes uniquely to the heterogeneity of cognitive impairment in LBD. Ann Neurol 2018; 1-13 ANN NEUROL 2019;85:259-271.
目的
利用数字组织病理学方法，在伴有痴呆的路易体障碍（LBD）患者的大型尸检队列中进行研究，以检验以下假设：并存的阿尔茨海默病（AD）病理学影响α-突触核蛋白（SYN）病理学的解剖分布，并存的 LBD 皮质tau 病理学与较差的认知表现相关，其分布模式与 AD 不同。
方法
研究了 55 例经尸检证实的 LBD（帕金森病伴痴呆，n=36；痴呆伴路易体，n=19）患者和 25 例 AD 患者。将 LBD 患者分为 AD 共病（SYN+AD=20 例）或无 AD 共病（SYN-AD=35 例）。比较了各组间皮质和皮质下/边缘区的 tau、β-淀粉样蛋白（Aβ）和 SYN 组织病理学的数字测量值，并与生前认知测试相关。
结果
在每个皮质区域，SYN+AD 的 SYN 负担均高于 SYN-AD（F=5.6-6.0，p＜0.02），但在海马旁回和纹状体中无差异（F=0.7-1.7，p＞0.2）。SYN+AD 在颞叶介导的命名任务上的表现不如 SYN-AD（t=2.1，p=0.04）。生前认知测试评分与 tau 负担呈负相关（r=-0.39 至-0.68，p＜0.05）。所有区域的 AD 患者 tau 水平均高于 SYN+AD（F=12.8-97.2，p＜0.001）；然而，SYN+AD 患者颞叶皮质中的 tau 比例高于 AD（t=2.0，p＜0.05），而 AD 患者额叶皮质中的 tau 比例高于 SYN+AD（t=3.3，p＜0.002）。SYN+AD 的皮质 Aβ 严重程度和分布与 AD 相似（F=1.6-2.0，p＞0.1）。
结论
伴有 AD 共病的 LBD 患者脑皮质中 SYN 病理学更为严重。皮质 tau 病理学与 LBD 痴呆患者的认知表现有关，其分布可能与单纯 AD 不同。tau 共病是 LBD 认知障碍异质性的独特贡献因素。Ann Neurol 2018；1-13 ANN NEUROL 2019；85：259-271.
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