阿尔茨海默病患者自身抗β淀粉样蛋白抗体的免疫特性和临床价值

The immunological features and clinical values of plasma autoantibodies to Aβ in elderly patients with Alzheimer's disease

目的探讨自身抗β淀粉样蛋白(Aβ)抗体在阿尔茨海默病(AD)和健康老年人中的发生率、免疫特性及其临床价值。方法采用109例 AD 患者和142例健康老年人的血浆对 Tg2576小鼠大脑切片进行免疫染色,并进行半定量的组织淀粉样蛋白免疫反应(TAPIR)测定。通过免疫沉降法,TAPIR 阳性和阴性血浆分别与人工合成的 Aβ和 AD 大脑抽提颗粒(FAβ)进行免疫沉降,沉降物经过电泳、转印迹,最后被 6E10标记。结果自身抗Aβ抗体频繁出现于 AD 患者(44.9%)和健康老年组(41.6%),两组差异无统计学意义;并与 AD 患者的痴呆程度和自然病程无关;它们与Aβ40和 FAβ具有更强的亲和力,与 Aβ42亲和性力弱。结论自身抗 Aβ抗体不能作为 AD 的生物学诊断标志,也不足以影响 AD 的临床症状和自然病程。

Objective To determine the positive rates of autoantibodies to Aβ in plasma of patients with Alzheimer＇s disease （AD） and healthy elderly subjects, to investigate the immunological features and their clinical values. Methods Plasma from 109 AD patients （AD group） and 142 age -matched normal controls （aNC group） were examined by tissue amyloid plaque immunoreactivity （TAPIR） assay. TAPIR positive and negative plasma were immunoprecipitated with synthetic Aβ40, Aβ42 peptides and formic acid-soluble fractions extracted from AD brain （FAβ）, the immunoprecipitates were detected by monoclonal anti-Aβ antibody 6E10 after being separated in 4 to 12 % NuPage Bis-Tris gel and transferred into polyvinylidene fluoride（PVDF）membranes to clarify the immunological features. To assess their values for clinical diagnosis and effects on AD natural course, the relationship between MMSE scores, illness durations and TAPIR were analysed. Results The Aβ autoantibodies were observed in both the AD （44.9%） and aNC groups （41.6%） but with no significant difference between the two groups （P 〉0.05）, and no significant relationship were observed between the Aβ autoantibody and the severity of dementia or the natural course. TAPIR positive plasma showed a stronger immunoaffinity with monomeric and dimeric Aβ40 and FAβ than with monomeric Aβ42, but a weak immunoaffinity with dimeric Aβ42. Conclusions Naturally existing plasma antibodies to Aβ might not be an useful biomarker for AD diagnosis, and could not affect clinical signs and natural progress of AD.