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目的采用免疫组织化学技术定量研究额颞叶变性(FTLD)和阿尔茨海默病(AD)病人大脑额叶的突触改变(突出素和SNAP-25)以及其与APOE基因型和MAPT单体型之间的关系。方法采用免疫组织化学方法检测3组(20例FTLD、10例AD和9例年龄匹配的正常人对照)尸解脑组织标本的额叶新皮质中突出素和SNAP-25的表达。结果与对照组和AD病人相比,FTLD病人的突出素表达显著增高,而SNAP-25表达显著降低(P<0.001)。FTLD中突出素上调是疾病特异性改变(P<0.000 1),不受年龄(P=0.787)或者皮质萎缩(P=0.248)影响。SNAP-25下调受多种因素的影响,包括家族史和FTLD的组织学特征、APOE基因型、MAPT单体型和性别。因此,SNAP-25下调在tau蛋白阴性、女性和无家族史的病人更为显著,FTLD病人APOEε4等位基因和MAPT H2单体型的出现显著影响突触蛋白的表达,特别是导致SNAP-25的表达降低。结论本研究提示:FTLD中突触蛋白的表达受多种遗传因素的影响,将来在探讨该疾病神经机制改变的神经病理和生化研究中需将这些因素考虑在内。FTLD中SNAP-25的选择性丢失可能与疾病本身某些关键但未被认知的临床特征密切相关。
Objective To quantitatively study the synaptic changes (prominences and SNAP-25) of the frontal lobe of frontal lobe of patients with frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD) by immunohistochemistry and its relationship with APOE genotype and MAPT monomer The relationship between types. Methods Immunohistochemistry was used to detect the expression of promonin and SNAP-25 in the neocortex of the frontal lobe in 3 groups (20 FTLD, 10 AD and 9 age-matched normal controls). Results Compared with the control group and AD patients, the expression of prominin in patients with FTLD was significantly increased, while the expression of SNAP-25 was significantly decreased (P <0.001). The up-regulation of prominence in FTLD is a disease-specific change (P <0.0001) independent of age (P = 0.787) or cortical atrophy (P = 0.248). SNAP-25 down-regulation is influenced by a number of factors, including family history and histological features of FTLD, APOE genotype, MAPT haplotype, and gender. Thus, SNAP-25 downregulation is more likely in tau-negative women and in patients with no family history, and the presence of APOE ε 4 alleles and MAPT H 2 haplotypes in FTLD patients significantly affects the expression of synapsin, particularly in SNAP-25 Decreased expression. Conclusions This study suggests that the expression of synapsins in FTLD is influenced by a number of genetic factors that will need to be taken into account in future neuropathological and biochemical studies that explore the neurological mechanisms underlying this disease. Selective loss of SNAP-25 in FTLD may be closely related to certain key but not recognized clinical features of the disease itself.