2026-05-18 コペンハーゲン大学（UCPH）
“It appears that the brain’s immune cells are dozy or exhausted, as if they have lost their ability to respond,” explains researcher behind new study. Illustration: University of Copenhagen
＜関連情報＞
- https://news.ku.dk/all_news/2026/05/garbage-collectors-of-the-brain-grind-to-a-halt-in-fatal-disease/
- https://www.nature.com/articles/s41467-026-71525-6
単一核脳トランスクリプトミクスにより、多系統萎縮症におけるミクログリア機能障害が明らかになった Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy
Rasmus Rydbirk,Frederik Nørby Friis Sørensen,Jonas Folke,Henriette Haukedal,Andrea Asenjo Martinez,Irene Lisa Vargas,Simone McGarry,Oline Chantell Hollmann,Camila Gherardelli,Sofia Sepulveda,Adam T. Szafran,Michael A. Mancini,Sanne Simone Kaalund,Tomasz Brudek,Lisette Salvesen,Sara Bech,Justyna Okarmus,Peter Kharchenko,Morten Meyer,Claudio Soto,Kristine Freude,Abhisek Mukherjee,Susana Aznar & Konstantin Khodosevich
Nature Communications Published:15 April 2026
DOI:https://doi.org/10.1038/s41467-026-71525-6 Unedited version
Abstract
Multiple system atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson’s disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology, we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Here, we show significant compositional differences in astroglia and microglia subtypes, while oligodendroglia and neurons are comparable. PD brains show abundant microglia expressing MHC class II HLA haplotypes, indicative of a proinflammatory state, alongside more homeostatic astrocytes. In contrast, MSA lack activated microglia but has more reactive astrocytes compared to PD. Transcriptomic analysis suggests compromised oligodendrocyte signaling in MSA, with microglia being in a state of immune tolerance or exhaustion. Microglia derived from iPSC exposed to patient cerebrospinal fluid exhibit reduced phagocytic activity, especially in MSA. These findings underscore a dysfunctional immune response in MSA as a potential contributor to the more severe pathophysiology of MSA.
