Leclercq P D, Murray L S, Smith C, Graham D I, Nicoll J A R, Gentleman S M
Division of Neuroscience and Psychological Medicine, Imperial College London, London W6 8RP, UK.
J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):229-33. doi: 10.1136/jnnp.2003.025528.
In view of the association of the apolipoprotein E (APOE) epsilon 4 allele with poor outcome after traumatic brain injury we determined the frequency of cerebral amyloid angiopathy (CAA) and the extent of haemorrhagic pathology in relation to APOE genotype in an autopsy series of 88 head injured cases.
Tissue sections from the frontal and temporal lobes were immunostained for amyloid-beta peptide (A beta) and stained for Congo red to identify vascular amyloid pathology. A semiquantitative assessment of contusions, the total contusion index, was used to estimate the severity of the haemorrhagic pathology. APOE genotypes were determined by polymerase chain reaction of genomic DNA extracted from paraffin embedded tissue sections.
CAA was present in 7/40 (18%) epsilon 4 carriers compared with 1/48 (2%) non-epsilon 4 carriers (p = 0.021, 95% confidence interval (CI) for difference in proportions with CAA 3% to 29%) with 6/40 (4 with CAA) epsilon 4 carriers being homozygotes. Thus the risk of having CAA for epsilon 4 carriers was 8.4 times that for the non-epsilon 4 carriers. However, there was no clear tendency for patients with CAA to have more severe or more numerous contusions (median contusion index 19 (CAA) v 14.5, p = 0.23, 95% CI for difference in medians -5 to 14).
Presence of CAA in head injured cases was significantly associated with possession of an APOE epsilon 4 allele but not with the severity of contusions.
鉴于载脂蛋白E(APOE)ε4等位基因与创伤性脑损伤后不良预后相关,我们在一个包含88例头部受伤病例的尸检系列中,确定了脑淀粉样血管病(CAA)的发生率以及与APOE基因型相关的出血性病变程度。
对额叶和颞叶的组织切片进行β淀粉样肽(Aβ)免疫染色以及刚果红染色,以识别血管淀粉样病变。采用挫伤的半定量评估方法,即总挫伤指数,来估计出血性病变的严重程度。通过对从石蜡包埋组织切片中提取的基因组DNA进行聚合酶链反应来确定APOE基因型。
40名ε4携带者中有7名(18%)存在CAA,相比之下,48名非ε4携带者中只有1名(2%)存在CAA(p = 0.021,CAA比例差异的95%置信区间(CI)为3%至29%),40名ε4携带者中有6名(4名伴有CAA)为纯合子。因此,ε4携带者患CAA的风险是非ε4携带者的8.4倍。然而,患有CAA的患者并无明显倾向于出现更严重或更多的挫伤(挫伤指数中位数19(CAA组)对14.5,p = 0.23,中位数差异的95%CI为-5至14)。
头部受伤病例中CAA的存在与APOEε4等位基因的携带显著相关,但与挫伤的严重程度无关。