Peripheral innate immunophenotype in neurodegenerative disease: blood-based profiles and links to survival.

Autor: Strauss A; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, UK., Swann P; Department of Psychiatry, University of Cambridge, Cambridge, UK., Kigar SL; Department of Psychiatry, University of Cambridge, Cambridge, UK.; Department of Medicine, University Cambridge, Cambridge, UK., Christou R; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, UK., Savinykh Yarkoni N; Department of Medicine, University Cambridge, Cambridge, UK., Turner L; Department of Psychiatry, University of Cambridge, Cambridge, UK.; Department of Medicine, University Cambridge, Cambridge, UK., Murley AG; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, UK., Chouliaras L; Department of Psychiatry, University of Cambridge, Cambridge, UK., Shapiro N; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, UK., Ashton NJ; Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.; Banner Alzheimer's Institute and University of Arizona, Phoenix, AZ, USA.; Banner Sun Health Research Institute, Sun City, AZ, USA., Savulich G; Department of Psychiatry, University of Cambridge, Cambridge, UK., Bevan-Jones WR; Department of Psychiatry, University of Cambridge, Cambridge, UK., Surendranthan A; Department of Psychiatry, University of Cambridge, Cambridge, UK., Blennow K; Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Zetterberg H; Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.; UK Dementia Research Institute at UCL, London, UK.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA., O'Brien JT; Department of Psychiatry, University of Cambridge, Cambridge, UK., Rowe JB; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, UK.; Medical Research Council Cognition and Brain Sciences Unit, Cambridge, UK., Malpetti M; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, UK. mm2243@medschl.cam.ac.uk.; UK Dementia Research Institute at University of Cambridge, Cambridge, UK. mm2243@medschl.cam.ac.uk.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Oct 29. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1038/s41380-024-02809-w
Abstrakt: The innate immune system plays an integral role in the progression of many neurodegenerative diseases. In addition to central innate immune cells (e.g., microglia), peripheral innate immune cells (e.g., blood monocytes, natural killer cells, and dendritic cells) may also differ in these conditions. However, the characterization of peripheral innate immune cell types across different neurodegenerative diseases remains incomplete. This study aimed to characterize peripheral innate immune profiles using flow cytometry for immunophenotyping of peripheral blood mononuclear cells in n = 148 people with Alzheimer's disease (AD), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), Lewy body dementia (LBD) as compared to n = 37 healthy controls. To compare groups, we used multivariate dissimilarity analysis and principal component analysis across 19 innate immune cell types. We identified pro-inflammatory profiles that significantly differ between patients with all-cause dementia and healthy controls, with some significant differences between patient groups. Regression analysis confirmed that time to death following the blood test correlated with the individuals' immune profile weighting, positively to TREM2+ and non-classical monocytes and negatively to classical monocytes. Taken together, these results describe transdiagnostic peripheral immune profiles and highlight the link between prognosis and the monocyte cellular subdivision and function (as measured by surface protein expression). The results suggest that blood-derived innate immune profiles can inform sub-populations of cells relevant for specific neurodegenerative diseases that are significantly linked to accelerated disease progression and worse survival outcomes across diagnoses. Blood-based innate immune profiles may contribute to enhanced precision medicine approaches in dementia, helping to identify and monitor therapeutic targets and stratify patients for candidate immunotherapies.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: