2025-07-21 ワシントン大学セントルイス校(WashU)
<関連情報>
- https://source.washu.edu/2025/07/blood-plasma-reveals-shared-pathways-in-neurodegenerative-diseases/
- https://www.nature.com/articles/s41591-025-03833-1
前頭側頭型認知症、アルツハイマー病、パーキンソン病における共有パスウェイと疾患特異的パスウェイ Shared and disease-specific pathways in frontotemporal dementia and Alzheimer’s and Parkinson’s diseases
Muhammad Ali,Buddhiprabha Erabadda,Yike Chen,Ying Xu,Katherine Gong,Menghan Liu,Alexa Pichet Binette,Jigyasha Timsina,Daniel Western,Chengran Yang,Gyujin Heo,Jacob W. Vogel,Betty M. Tijms,Varsha Krish,Farhad Imam,The Global Neurodegeneration Proteomics Consortium (GNPC),Oskar Hansson,Laura Winchester & Carlos Cruchaga
Nature Medicine Published:15 July 2025
DOI:https://doi.org/10.1038/s41591-025-03833-1
Abstract
Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and frontotemporal dementia (FTD), exhibit distinct yet overlapping pathological mechanisms. Leveraging large-scale plasma proteomics data from the Global Neurodegeneration Proteomics Consortium, we analyzed 10,527 plasma samples (1,936 AD, 525 PD, 163 FTD, 1,638 dementia and 6,265 controls) to identify disease-specific and shared proteins across NDs. We identified 5,187 proteins significantly associated with AD, 3,748 with PD and 2,380 with FTD that revealed both common and divergent proteomic signatures, which were confirmed by multiple analytical approaches and orthogonal validation. PD and FTD showed the highest overlap (r2 = 0.44) and AD and PD the least (r2 = 0.04). Immune system, glycolysis, and matrisome-related pathways were enriched across all NDs, while disease-specific pathways included apoptotic processes in AD, endoplasmic reticulum–phagosome impairment in PD and platelet dysregulation in FTD. Network analysis identified key upstream regulators (RPS27A in AD, IRAK4 in PD and MAPK1 in FTD) potentially driving these proteomic changes. These findings reveal distinct and shared mechanisms across NDs, highlighting potential regulatory proteins and pathways for diagnostic and therapeutic strategies in neurodegeneration.
