Neuropathologic characteristics of familial Alzheimer disease : cotton wool plaques and neuronal migration

棉絮斑（CWP）是一种病理改变，最初报道与变异型阿尔茨海默病（早发性痴呆和痉挛性轻瘫）相关，由早老素1（PSEN 1）基因外显子9缺失引起。本研究的目的是报告8例早发性阿尔茨海默病（EOAD）和与早老素1（PSEN 1）基因突变L166 P、G217 D、V261 F、V261 I、P264 L和A431 E相关的“棉絮斑（CWP）”患者的临床和神经病理学特征。为了评估EOAD-CWP的临床特征，我们分析了包括痉挛性下肢轻瘫在内的几种症状。此外，使用CERAD方法半定量评估多个解剖区域（如大脑皮质、皮质下核、小脑和脑干）中CWP和神经炎斑块（NP）的频率。每个切片使用苏木精和伊红，Bielschowsky和/或Bodian方法染色， ...更多信息 使用抗Aβ、tau和α-突触核蛋白的抗体进行免疫标记。此外，分析了大脑白色物质中的神经元迁移异常。所有病例的临床特征均为早发性痴呆，但痉挛性轻瘫仅见于L166 P和V261 F突变病例。神经病理学上，在大脑皮质、纹状体和杏仁核中观察到大量CWP。在5个突变（L166 P、G217 D、V261 F、V261 I、A431 E）中，CWP的频率显著高于NP。在某些情况下，在大脑白色物质中观察到异常神经元。除了痴呆，临床表现是异质性的，痉挛性轻瘫不是EOAD-CWP的强制性症状。CWP的分布不同于NPs的分布，在NPs中CWP延伸到纹状体和中脑。如果存在CWP，它们通常是大脑中斑块的最常见形式。本研究结果可为EOAD-CWP的临床和神经病理异质性提供信息。(297减

Cotton wool plaque (CWP) is a pathologic alteration initially reported in association with variant Alzheimer disease (early onset of dementia and spastic paraparesis) caused by a deletion of exon 9 in the Presenilin 1 (PSEN1) gene. The aim of this study is to report the results of clinical and neuropathologic characteristics of eight individuals affected with early onset of Alzheimer disease (EOAD) and 'cotton wool plaques (CWPs)' in association with mutations L166P, G217D, V261F, V261I, P264L and A431E in the Presenilin 1 (PSEN1) gene. In order to appraise the clinical characteristics of EOAD-CWPs, we analyzed several symptoms that include spastic paraparesis. In addition, the frequency of CWPs and neuritic plaques (NPs) was assessed using the semi quantification of the CERAD methodology in the multiple anatomical regions such as cerebral cortex, subcortical nucleus, cerebellum and brainstem. Each section was stained using hematoxylin and eosin, Bielschowsky and/or Bodian methods as w … More ell as immunolabeled using antibodies raised against Aβ, tau and α-synuclein. In addition, neuronal migration abnormalities were analyzed in the cerebral white matter. All cases were characterized clinically by early onset of dementia, however spastic paraparesis was only found in cases with L166P and V261F mutation. Neuropathologically, numerous CWPs were seen in the cerebral cortex, striatum and amygdala. The frequency of CWPs was significantly higher than that of NPs in five mutations (L166P, G217D, V261F, V261I, A431E). In some instances, abnormal neurons were seen in the cerebral white matter. Besides dementia, clinical presentation is heterogeneous and spastic paraparesis is not obligatory symptoms in EOAD-CWPs. The distribution of CWPs differs from that of NPs in which it extends to the striatum and midbrain. If CWPs are present, they are generally severest modality of plaques in the cerebrum. Our results may provide the information of clinical and neuropathologic heterogeneities of EOAD-CWPs. (297 words) Less