2026-05-29 中国科学院（CAS）
＜関連情報＞
- https://english.cas.cn/newsroom/cas-in-media/202605/t20260529_1160074.shtml
- https://www.cell.com/cell/abstract/S0092-8674(26)00517-9
TPPP/p25アミロイドシード活性は多系統萎縮症の特異的バイオマーカーである TPPP/p25 amyloid seeding activity as a specific biomarker for multiple system atrophy
Shuyi Zeng (曾姝怿) ∙ Shenqing Zhang (章沈庆) ∙ Shengnan Zhang (张胜男) ∙ … ∙ Jian Wang (王坚) ∙ Cong Liu (刘聪) ∙ Dan Li (李丹)
Cell Published:May 26, 2026
DOI:https://doi.org/10.1016/j.cell.2026.04.050
Graphical abstract
Highlights
- Native TPPP/p25 is intrinsically self-protected from amyloid aggregation
- Cryo-EM reveals conformational remodeling of the CORE during amyloid assembly
- TPPP/p25 amyloid seeds in CSF serve as a specific biomarker for MSA
- Seed amplification assays can differentiate MSA from related neurodegenerative diseases
Summary
Detection of α-synuclein (α-syn) amyloid seeds in human biofluids has attracted great interest for clinical diagnosis of synucleinopathies. However, as a common biomarker, α-syn lacks specificity in reliably differentiating distinct disorders. Here, we report tubulin polymerization promoting protein (TPPP/p25) as a cerebrospinal fluid (CSF) biomarker for the specific diagnosis of multiple system atrophy (MSA). We demonstrate that native TPPP/p25 is self-protected against amyloid aggregation, while disease-related mutation disrupts this protection, triggering TPPP/p25 aggregation. Cryo-electron microscopy (cryo-EM) analysis reveals that the well-folded core domain (CORE) undergoes large conformational changes to mediate amyloid formation. Based on this insight, we developed a seed amplification assay using a minimized CORE (miniCORE) monomer, which detects TPPP/p25 amyloid seeds in CSF and robustly differentiates MSA from Parkinson’s disease (PD) and other neurodegenerative diseases. Our findings establish misfolded TPPP/p25 as a promising, specific biomarker in biofluids for MSA diagnosis.
