J Alzheimers Dis. 2018;64(3):751-760. doi: 10.3233/JAD-180039.
Unlike antibodies against amyloid-β, little is known about serum antibodies to neuron-specific cytoskeletal proteins in patients with Alzheimer's disease (AD).
We aimed to study IgG autoantibodies against tau protein, light (NFL) and heavy subunits (NFH) of neurofilaments in serum of AD patients and elderly controls and to explore the evolution of antineurocytoskeletal antibody levels over time.
Antibodies against three targets (tau, NFL, and NFH) were measured using ELISA in 100 serum samples from 51 cognitively normal elderly controls and 49 patients with AD. Our primary cross-sectional design was further extended to monitor fluctuations over 1-2 years in a subset of individuals.
The AD patients had lower levels of anti-tau antibodies (p = 0.03) and even lower anti-NFH antibodies (p = 0.005) than those in the control group at baseline. On the contrary, anti-NFL antibodies or total IgG concentrations in serum did not differ. All three antibodies remained stable in both groups except for a selective and significant anti-tau decline in AD patients (p = 0.03).
The different responses to these antigens suggest some antibody selectivity in AD. The significant decline was observed for only serum anti-tau antibodies in AD patients over time and it corresponds to lower anti-tau levels in these patients. Our findings indicate a special feature of disease-relevant antigens and humoral autoimmunity in AD.
与针对淀粉样蛋白-β的抗体不同，针对阿尔茨海默病（AD）患者神经元特异性细胞骨架蛋白的血清抗体知之甚少。
我们旨在研究 AD 患者和老年对照组血清中针对微管相关蛋白 tau、轻（NFL）和重（NFH）神经丝的 IgG 自身抗体，并探讨抗神经细胞骨架抗体水平随时间的演变。
使用 ELISA 法在 100 份来自 51 名认知正常的老年对照组和 49 名 AD 患者的血清样本中测量了针对这三个靶标的抗体（tau、NFL 和 NFH）。我们的初步横断面设计进一步扩展到监测部分个体 1-2 年内的波动。
AD 患者的抗 tau 抗体水平较低（p = 0.03），甚至抗 NFH 抗体水平也较低（p = 0.005），基线时与对照组相比。相反，血清中抗 NFL 抗体或总 IgG 浓度没有差异。除 AD 患者的抗 tau 抗体选择性显著下降（p = 0.03）外，两组所有三种抗体均保持稳定。
对这些抗原的不同反应表明 AD 中存在一些抗体选择性。AD 患者仅在血清抗 tau 抗体随时间呈显著下降，且与这些患者的抗 tau 水平较低相对应。我们的发现表明 AD 中与疾病相关的抗原和体液自身免疫具有特殊特征。
