Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles
Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles
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DOI：
10.1007/s00401-006-0136-y
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发表时间：
2007-01-01
影响因子：
12.7
通讯作者：
Roher, Alex E.
中科院分区：
文献类型：
--
作者：
Beach, Thomas G.;Wilson, Jeffrey R.;Roher, Alex E.
自上个世纪的第一个十年以来，颅内动脉粥样硬化在阿尔茨海默病（AD）中的作用一直是一个争论的主题。在一系列世纪中期大体解剖学尸检研究表明颅内动脉粥样硬化和老年痴呆之间的关系不稳定后，最初的AD "血管假说"被拒绝。然而，这些早期研究没有使用统计学方法，研究者似乎没有考虑颅内动脉粥样硬化对AD风险可能具有概率而非绝对影响的可能性。最近三个独立研究小组的研究发现，死后测量Willis动脉粥样硬化环和AD之间存在显著的统计学相关性。本研究旨在进一步探讨这种关联在大型尸检系列中的有效性，包括神经病理学诊断为血管性痴呆（VaD）和非AD痴呆的病例。对397例经神经病理学诊断的正常老年人（对照组92例，AD组215例，VaD组30例，非AD组60例）进行Willis环动脉粥样硬化大体解剖分级。Willis环动脉粥样硬化在AD和VaD患者中比对照组更严重，而在对照组和非AD痴呆患者中相当。动脉粥样硬化分级增加AD和VaD诊断的优势比（OR），也增加了神经炎斑块密度增加和Braak神经系统缠结分期升高的OR。在考虑了年龄、性别和载脂蛋白E-E4等位基因的影响后，这些相关性的显著性仍然存在。结果表明，颅内动脉粥样硬化和AD之间的统计学相关性不是诊断错误分类或载脂蛋白E-PD4等位基因分布不均的人为因素。
The role of intracranial atherosclerosis in Alzheimer's disease (AD) has been a subject of debate since the first decade of the last century. The initial "vascular hypothesis" of AD was rejected after a series of mid-twentieth century gross anatomical postmortem studies that showed an inconstant relationship between intracranial atherosclerosis and senile dementia. These early studies did not utilize statistical methods, however, and the investigators did not appear to consider the possibility that intracranial atherosclerosis might have a probabilistic, rather than an absolute, effect on AD risk. Recent studies by three independent groups have found a significant statistical association between postmortem measures of circle of Willis atherosclerosis and AD. The present study was undertaken to further address the validity of this association in a large autopsy series, including cases diagnosed neuropathologically with vascular dementia (VaD) and non-AD dementias. Postmortem gross anatomical grading of circle of Willis atherosclerosis was performed in 397 subjects classified by neuropathological diagnosis, including 92 non-demented elderly controls, 215 with AD, 30 with VaD and 60 with non-AD dementias. Circle of Willis atherosclerosis was more severe in subjects with AD and VaD than in control subjects, while it was equivalent between control subjects and subjects with non-AD dementias. Increasing atherosclerotic grade increased the odds ratios (OR) for the diagnoses of both AD and VaD and also increased the ORs for both increased neuritic plaque density and higher Braak neurofibrillary tangle stage. The significance of these associations was retained after consideration of the effects of age, gender and the apolipoprotein E-epsilon 4 allele. The results suggest that the statistical association between intracranial atherosclerosis and AD is not an artifact of diagnostic misclassification or of unequal distribution of the apolipoprotein E-epsilon 4 allele.