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

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dc.creatorStrauss, Alexandra
dc.creatorSwann, Peter
dc.creatorKigar, Stacey L
dc.creatorChristou, Rafailia
dc.creatorSavinykh Yarkoni, Natalia
dc.creatorTurner, Lorinda
dc.creatorMurley, Alexander G
dc.creatorChouliaras, Leonidas
dc.creatorShapiro, Noah
dc.creatorAshton, Nicholas J
dc.creatorSavulich, George
dc.creatorBevan-Jones, W Richard
dc.creatorSurendranthan, Ajenthan
dc.creatorBlennow, Kaj
dc.creatorZetterberg, Henrik
dc.creatorO'Brien, John T
dc.creatorRowe, James B
dc.creatorMalpetti, Maura
dc.date2025-04-22T14:53:09Z
dc.date2025-05
dc.date2024-01-16
dc.date2025-04-22T14:53:09Z
dc.date.accessioned2026-08-03T01:58:37Z
dc.descriptionFunder: This study was co-funded by the Dementias Platform UK and Medical Research Council (MC_UU_00030/14; MR/T033371/1); the Wellcome trust (103838; 220258); Race Against Dementia Alzheimer’s Research UK (ARUK-RADF2021A-010); the Cambridge University Centre for Parkinson-Plus (RG95450); the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014; NIHR203312: the views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care); the Progressive Supranuclear Palsy Association (PSPA2022/SMALL GRANTS002); the Addenbrookes Charitable Trust (Ref: 900380). HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, and Swedish State Support for Clinical Research (#ALFGBG-71320).
dc.descriptionThe 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.
dc.descriptionThis study was co-funded by the Dementias Platform UK and Medical Research Council (MC_UU_00030/14; MR/T033371/1); Race Against Dementia Alzheimer’s Research UK (ARUK-RADF2021A-010); the Wellcome trust (103838; 220258); the Cambridge University Centre for Parkinson-Plus (RG95450); the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014; NIHR203312: the views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care); the Progressive Supranuclear Palsy Association (PSPA2022/SMALL GRANTS002); the Addenbrookes Charitable Trust (Ref: 900380). HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, and Swedish State Support for Clinical Research (#ALFGBG-71320).
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dc.identifier1359-4184
dc.identifiers41380-024-02809-w
dc.identifier2809
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/383157
dc.identifier1476-5578
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/162118
dc.languageen
dc.languageeng
dc.publisherSpringer Nature
dc.publisherhttps://doi.org/10.1038/s41380-024-02809-w
dc.subjectHumans
dc.subjectMale
dc.subjectFemale
dc.subjectNeurodegenerative Diseases
dc.subjectAged
dc.subjectImmunity, Innate
dc.subjectMiddle Aged
dc.subjectAlzheimer Disease
dc.subjectMonocytes
dc.subjectImmunophenotyping
dc.subjectFrontotemporal Dementia
dc.subjectLeukocytes, Mononuclear
dc.subjectAged, 80 and over
dc.subjectFlow Cytometry
dc.subjectSupranuclear Palsy, Progressive
dc.subjectLewy Body Disease
dc.titlePeripheral innate immunophenotype in neurodegenerative disease: blood-based profiles and links to survival.
dc.typeArticle

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