Tian J, Shi J, Bailey K, Lendon C L, Pickering-Brown S M, Mann D M A
Clinical Neuroscience Research Group, University of Manchester, Hope Hospital, Salford, Manchester M6 8HD, UK.
J Neurol Neurosurg Psychiatry. 2004 May;75(5):696-9. doi: 10.1136/jnnp.2003.012096.
To investigate the association between white matter damage, as evidenced by myelin loss (ML), the extent of cerebral amyloid angiopathy (CAA), or arteriosclerosis (Art), and apolipoprotein E (ApoE) e4 allele in Alzheimer's disease (AD), in order to understand the causes of damage to white matter in AD and its contribution to the pathogenesis of the disorder.
Brain tissues were obtained from 94 patients with AD confirmed by autopsy. ApoE genotyping was performed by PCR on DNA extracted from frontal cortex or cerebellum. CAA and Art were assessed on Weigert's haematoxylin and eosin stained sections in frontal, temporal, parietal, and occipital cortices; the extent of ML was scored on Luxol fast blue stained sections of these regions.
The ApoE e4 allele frequency in the 61 patients with ML was not significantly different from that in the 33 patients without ML, nor did this differ in the 84 patients with Art from that in the 10 patients without Art. There were no significant differences in the proportions of patients with genotypes containing 0, 1, or 2 ApoE e4 alleles in the presence or absence of ML or Art. The mean ML, Art, or CAA scores within each region, and the total scores summed across all four brain regions, did not differ between patients with 0, 1, or 2 ApoE e4 alleles. However, the mean ML severity score in the occipital cortex was significantly greater than that in the frontal or temporal cortices in patients with 1 or 2 ApoE e4 alleles. The severity of CAA in the occipital cortex was significantly higher than that in other areas of cortex in patients with 0 or 2 ApoE e4 alleles. The mean Art score in the occipital cortex was greater than that in the temporal cortex in patients with two ApoE e4 alleles and was higher than that in the frontal cortex in patients with one ApoE e4 allele.
The likelihood of patients with AD suffering from CAA, Art, or ML is not influenced by ApoE e4 allele, nor is the overall burden of these pathological changes in the brain. However, the distribution of ML, CAA, and Art within the brain is at least partly influenced by genotype and dosage of ApoE e4 allele, with the occipital cortex being more severely affected by all of these pathological changes in e4 allele bearers, particularly when two ApoE e4 alleles are present.
研究以髓鞘丢失（ML）、脑淀粉样血管病（CAA）程度或动脉硬化（Art）为证据的白质损伤与阿尔茨海默病（AD）中载脂蛋白E（ApoE）e4等位基因之间的关联，以了解AD中白质损伤的原因及其对该疾病发病机制的作用。
从94例经尸检确诊为AD的患者获取脑组织。通过对从额叶皮质或小脑提取的DNA进行聚合酶链反应（PCR）来进行ApoE基因分型。在额叶、颞叶、顶叶和枕叶皮质的魏格特苏木精和伊红染色切片上评估CAA和Art；在这些区域的Luxol固蓝染色切片上对ML程度进行评分。
61例有ML的患者中ApoE e4等位基因频率与33例无ML的患者相比无显著差异，84例有Art的患者与10例无Art的患者相比也无差异。在有或无ML或Art的情况下，含0、1或2个ApoE e4等位基因的基因型患者比例无显著差异。在含0、1或2个ApoE e4等位基因的患者中，每个区域的平均ML、Art或CAA评分以及四个脑区总和的总分无差异。然而，在有1个或2个ApoE e4等位基因的患者中，枕叶皮质的平均ML严重程度评分显著高于额叶或颞叶皮质。在有0个或2个ApoE e4等位基因的患者中枕叶皮质的CAA严重程度显著高于皮质其他区域。在有2个ApoE e4等位基因的患者中枕叶皮质的平均Art评分高于颞叶皮质，在有1个ApoE e4等位基因的患者中高于额叶皮质。
AD患者患CAA、Art或ML的可能性不受ApoE e4等位基因影响，大脑中这些病理变化的总体负担也不受影响。然而，ML、CAA和Art在脑内的分布至少部分受ApoE e4等位基因的基因型和剂量影响，枕叶皮质在携带e4等位基因的患者中受所有这些病理变化的影响更严重，特别是当存在两个ApoE e4等位基因时。
