Lehtovirta M, Kuikka J, Helisalmi S, Hartikainen P, Mannermaa A, Ryynänen M, Soininen H
Department of Neurology, Kuopio University Hospital and University of Kuopio, Finland.
J Neurol Neurosurg Psychiatry. 1998 Jun;64(6):742-6. doi: 10.1136/jnnp.64.6.742.
In mild Alzheimer's disease, SPECT imaging of regional cerebral blood flow has highlighted deficits in the posterior association cortex, and later in the disease process, the deficit spreads to involve the frontal cortex. The sigma4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. The effect of apolipoprotein E polymorphism on cerebral perfusion was studied. The hypothesis was that those patients with Alzheimer's disease who carry the sigma4 allele would have more severe cerebral hypoperfusion.
Thirty one patients with Alzheimer's disease and eight age and sex matched control subjects were examined in a three year longitudinal study. Patients with Alzheimer's disease were divided into subgroups according to their number of sigma4 alleles. Regional cerebral blood flow ratios referred to the cerebellum were examined by 99mTc-HMPAO SPECT. Apolipoprotein E genotypes were determined by digestion of polymerase chain reaction products with the restriction enzyme Hha1.
All patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion compared with control subjects. The two sigma4 allele subgroups had the lowest ratios at the baseline assessment in the parietal and occipital cortices, and at the follow up in the temporal, parietal, and occipital cortices. They had the highest reduction in percentage terms in the temporal and occipital cortices compared with the other subgroups. However, the global clinical severity did not differ at the baseline or follow up examinations between the subgroups.
Apolipoprotein E polymorphism is involved in the pathogenesis and heterogeneity of Alzheimer's disease as the most severe cerebral hypoperfusion was found in the sigma4 allele subgroups. This might have implications for therapeutic approaches in Alzheimer's disease.
在轻度阿尔茨海默病中，局部脑血流的单光子发射计算机断层扫描（SPECT）成像突出显示了后联合皮质的缺陷，并且在疾病后期，该缺陷会扩散至额叶皮质。载脂蛋白E的ε4等位基因是阿尔茨海默病的一个风险因素。研究了载脂蛋白E基因多态性对脑灌注的影响。假设是携带ε4等位基因的阿尔茨海默病患者会有更严重的脑灌注不足。
在一项为期三年的纵向研究中，对31例阿尔茨海默病患者和8名年龄及性别匹配的对照受试者进行了检查。阿尔茨海默病患者根据其ε4等位基因的数量分为亚组。通过99m锝-六甲基丙烯胺肟（99mTc-HMPAO）SPECT检查相对于小脑的局部脑血流比值。通过用限制性内切酶Hha1消化聚合酶链反应产物来确定载脂蛋白E基因型。
与对照受试者相比，所有阿尔茨海默病患者均存在双侧颞顶叶灌注不足。两个ε4等位基因亚组在基线评估时顶叶和枕叶皮质的比值最低，在随访时颞叶、顶叶和枕叶皮质的比值最低。与其他亚组相比，它们在颞叶和枕叶皮质的百分比降低幅度最大。然而，亚组之间在基线或随访检查时的整体临床严重程度并无差异。
载脂蛋白E基因多态性参与了阿尔茨海默病的发病机制和异质性，因为在ε4等位基因亚组中发现了最严重的脑灌注不足。这可能对阿尔茨海默病的治疗方法有影响。
