This review considers whether the Braak hypothesis on protein propagation could account for prion disease, particularly Creutzfeldt–Jakob disease (CJD). In CJD, we can speculate on the pathological onset region to some degree in reference to the clinical symptoms and magnetic resonance imaging findings. Although relating the Braak hypothesis to prion disease is not straightforward, the following could be proposed based on experimental and previously reported case observations. Pathogenic abnormal prion protein (PrP) deposition in the central nervous system (CNS) probably begins several months or years before clinical symptom onset, signifying the potentiality of a preclinical stage, similar to α‐synuclein deposition in Parkinson's disease (PD) and amyloid‐β/tau deposition in Alzheimer's disease (AD). Unlike in PD and AD, the initial clinical symptoms of CJD vary by case, and thus the onset lesions must also be various and multiple in the CNS. Based on the pathological findings, particularly of PrP deposition extensively observed in the CNS gray matter of autopsy cases, it could be speculated that in the early disease stage, including the preclinical stage, abnormal PrP spreads from the onset region without directionality or hierarchy. Because each CNS region shows either vulnerability to or resistance against PrP deposition and pathological progression in prion disease, the lesion distribution shows system degeneration. Although pathologically combined cases of type 1 and type 2 PrP patterns are often recognized, type 1 and type 2 PrP patterns must never shift toward each other during the disease course; in other words, the original type of PrP deposition in each region presumably remains unchanged in each case. According to the several observations and corresponding speculations, there are at least partial similarities between prion disease and protein propagation, as explained by the Braak hypothesis, in terms of pathological lesion progression, but several noted contradictions preclude the hypothesis from comprehensively accounting for prion disease.

中文翻译：

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朊病毒病的 Braak 假说，重点是克雅氏病

本综述考虑了关于蛋白质繁殖的 Braak 假说是否可以解释朊病毒病，尤其是克雅氏病 (CJD)。在CJD中，我们可以参考临床症状和磁共振成像结果，在一定程度上推测病理起病区域。尽管将 Braak 假设与朊病毒病联系起来并不简单，但可以根据实验和先前报告的病例观察提出以下建议。中枢神经系统 (CNS) 中的致病性异常朊病毒 (PrP) 沉积可能在临床症状出现前几个月或几年开始，这表明临床前阶段的潜力，类似于帕金森病 (PD) 和淀粉样蛋白中的 α-突触核蛋白沉积阿尔茨海默病 (AD) 中的 β/tau 沉积。与 PD 和 AD 不同的是，CJD 的初始临床症状因病例而异，因此中枢神经系统的起病病变也一定是多种多样的。根据病理结果，特别是在尸检病例的 CNS 灰质中广泛观察到的 PrP 沉积，可以推测在疾病早期阶段，包括临床前阶段，异常的 PrP 从发病区域扩散，没有方向性或层次性。由于每个中枢神经系统区域都表现出对朊病毒病中 PrP 沉积和病理进展的易感性或抵抗性，因此病变分布显示系统退化。尽管通常会发现 1 型和 2 型 PrP 模式的病理组合病例，但在病程中，1 型和 2 型 PrP 模式绝不能相互转移；换句话说，在每种情况下，每个区域的原始 PrP 沉积类型可能保持不变。根据几个观察和相应的推测，朊病毒病和蛋白质传播之间至少有部分相似之处，正如 Braak 假说所解释的，在病理病变进展方面，但几个明显的矛盾使该假说无法全面解释朊病毒病。