大疱性类天疱疮（Bullous Pemphigoid, BP）是好发于老年人的严重自身免疫性大疱病，常合并神经退行性疾病（包括阿尔兹海默病（Alzheimer’s disease, AD）、帕金森病（Parkinson’s disease, PD）等），具体机制不明。我们的前期工作发现，AD、PD患者血清中存在与对照组有显著性差异的BP抗体致病片段，且预实验中已提取出部分AD、PD、BP患者血清中的外泌体。我们猜测，AD、PD患者的BP自身抗体由外泌体作为载体运输到血液中，在适当条件下释放而导致BP发生。本研究拟对AD、PD、BP患者血清、脑脊液中的外泌体进行鉴定、对其携带的miRNA及蛋白进行分析、通过细胞学实验与动物实验，检测外泌体影响下正常人角质形成细胞炎症通路及人源化BP模型鼠的血清学、皮肤、脑组织改变，验证外泌体对AD及PD患者的致BP作用，阐释神经退行性疾病合并BP的机制。

Bullous pemphigoid (BP) is a severe autoimmune blistering disease that has a predilection on the elderly. Our previous study has demonstrated an increase of anti-BP antibody in patients with neurodegenerative diseases including Alzheimer’s disease (AD) or Parkinson’s disease (PD), significantly higher pathogenic segments of anti-BP antibodies can be found in serums of AD and PD patients. Our pilot study found exosomes in AD and PD patients’ serum. All above led us to the hypothesis that anti-BP antibodies could be transported by exosomes in AD and PD patients’ blood and release at certain condition that finally made BP happens..Our study is going to illustrate the mechanism of the exosomes in AD/PD patients. Exosomes would be extracted from AD, PD, BP patients’ and healthy people’s serums & cerebrospinal fluid, and be identified using several typical techniques. Characteristics of protein in the exosomes would be analyzed including epitope spreading, subtype of IgG and the affinity of antibodies. Immunological changes would be detected in exosome-treated human keratinocytes. In vivo, humanized BP mouse model would be treated with exosomes and changes of the mice’s skin, brain and serum would finally be collected. By verifying the pathogenic role of anti-BP antibodies from exosomes in AD and PD patients, we manage to further illustrate the relationship between neurodegeneration and BP.