【摘要】 目的通过比较有无自身抗Aβ抗体的阿尔茨海默病(AD)患者和年龄匹配的健康老年对照者(aNC)血浆Aβ水平之间差异,研究自身抗Aβ抗体对血浆Aβ水平的影响。方法113例AD患者和155例aNC的血浆对Tg2576小鼠大脑组织连续切片进行免疫染色,并进行组织淀粉样蛋白免疫反应(TAPIR)测定。随后,TAPIR阳性和阴性血浆分别与人工合成的Aβ40、Aβ42进行免疫沉降,免疫沉降物经过western blot检测分析其免疫特性。最后通过一种双抗体夹心的ELISA精确定量所有血浆的Aβ水平。结果(1)自身抗Aβ抗体无差异地频繁出现于AD患者(45．1%)和aNC中(41．3%)(P＞0．05),并在免疫沉降过程中表现出与Aβ40更强的亲和力。(2)两组TAPIR+和TAPIR-血浆的Aβ40和Aβ42水平比较均无显著性差异(P＞0．05)。结论自身抗Aβ抗体不足以影响血浆Aβ水平,人类抗Aβ抗体产生和作用机制可能有别于转基因AD动物模型。更多还原

【Abstract】 Objective To investigate the effect of autoantibodies to Aβon plasma level of Aβthrough analyzing the Aβlevels in plasma with or without autoantibodies between patients with Alzheimer’s disease(AD)and age-matched normal controls(aNCs).Methods Plasma from 113 AD cases and 155 aNCs were employed to make a special tissue amyloid plaque immunoreactivity(TAPIR)assay by immunostaining of paraffin-embedded serial sections of Tg2576 mouse brain tissues;TAPIR(+) and TAPIR (-)plasma were immunoprecipitated with synthetic Aβ40 and Aβ42 peptides.The immunoprecipitates were transferred into PVDF membranes in order to clarify the immunological features of plasma autoantibodies to Aβ.Finally,the plasma levels of Aβ40 and Aβ42 were quantitatively analyzed by sandwich ELISA. Results The plasma autoantibodies to Aβfrequently occurred in both AD patients(45.1%)and aNCs (41.3%),showing a stronger affinity with Aβ40 during the immunoprecipitation.No significant difference in the occurrence rates was found between AD patients and aNCs(P＞0.05).There was no significant difference in Aβ40 and Aβ42 levels between TAPIR(+)and TAPIR(-)plasma.Conclusion The plasma autoantibodies to Aβcould not make obvious effects on the plasma level of Aβ.Combined with previous findings,our data suggested that the mechanisms and pathogenesis of antibodies to Aβin human should be much different from that in transgenic animal model of AD.更多还原