时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
First described in 2008 () as a distinct entity among sporadic disease forms, with less than 150 cases reported worldwide to date (; ; ; ; ; ; ; ; , ; ; ; ; ; ; , ; ; ; ), the clinical diagnosis remains challenging.；This, along with slower disease progression, might also explain why examination of 14-3-3 protein in the CSF often remains negative.；We discuss the diagnostic challenges and review current literature.
方法
Hematoxylin-eosin and luxol fast blue/nuclear fast red staining as well as immunohistochemistry were performed on selected regions.；The amplification protocol consisted of an initial denaturation step at 95 °C for 15 min, followed by a touchdown PCR phase of 10 cycles.；To confirm the RFLP results and screen the entire coding sequence for rare variants or mutations, bidirectional Sanger sequencing was conducted.；Prior to sequencing, PCR products were purified using Qiaquick Gel Extraction Kit (Qiagen, Hilden, Germany) to remove residual primers and dNTPs.
核心结论
The neurological examination revealed a mild rigidity, postural instability, diffuse muscle weakness in upper and lower limbs, accentuated tendon reflexes in the right lower limb, right-sided bradydiadochokinesia, bilateral impaired coordination on the finger-to-nose-test.；A new MRI showed cortical diffusion restriction in the left occipital lobe and left thalamus with no corresponding FLAIR abnormality, suggesting an acute infarct, which was not confirmed in subsequent MRI.；She was referred to the Department of Neurology in October 2022 because of worsening of the memory impairment in the last 6 months associated with language alteration. ‖ 结论：In conclusion, VPSPr is a challenging clinical and neuropathological condition.
局限
The lack of cerebellar PrP deposits in patient 1 made the VPSPr diagnosis challenging.；A lack of micro-plaques in the cerebellum has also been reported previously (; ; ).；The lack of cerebellar involvement seems, therefore, to be influenced by the codon 129 polymorphism and the presence of methionine.
对本项目的价值
★☆☆☆☆ 脑老化是最大未满足需求，也是终点最难量化的领域；biomarker 与认知读数选择最敏感。
全文来源
PMC JATS 全文（正文 27,239 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Variably protease-sensitive prionopathy in the context of a complex proteinopathy: clinical and neuropathological challenges.
- 期刊与标识：Front Neurosci · PMID 42953028 · DOI 10.3389/fnins.2026.1950078
B 级证据分级：B 级（同行评议临床前研究，主要为动物模型）
本文核心结论来自动物模型或体外细胞学，属临床前证据，不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义，与人类临床结局之间仍有距离。
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