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.

先天免疫系统在许多神经退行性疾病的进展中起着不可或缺的作用。除了中枢先天免疫细胞（例如小胶质细胞）外，外周先天免疫细胞（例如血液单核细胞、自然杀伤细胞和树突状细胞）在这些情况下也可能有所不同。然而，不同神经退行性疾病中外周先天免疫细胞类型的表征仍然不完整。本研究旨在使用 流式细胞术对 n = 148 名阿尔茨海默病 （AD）、额颞叶痴呆 （FTD）、皮质基底节综合征 （CBS）、进行性核上性麻痹 （PSP）、路易体痴呆 （LBD） 患者进行外周血单核细胞免疫表型分析，与 n = 37 名健康对照者相比。为了比较各组，我们对 19 种先天免疫细胞类型使用了多变量差异分析和主成分分析。我们确定了全因痴呆患者和健康对照者之间显著不同的促炎特征，患者组之间存在一些显著差异。回归分析证实，血液检测后的死亡时间与个体的免疫特征权重相关，与 TREM2+ 和非经典单核细胞呈正相关，与经典单核细胞呈负相关。综上所述，这些结果描述了跨诊断的外周免疫特征，并强调了预后与单核细胞细分和功能之间的联系（通过表面蛋白表达测量）。 结果表明，血液来源的先天免疫谱可以告知与特定神经退行性疾病相关的细胞亚群，这些细胞与疾病加速和诊断中较差的生存结果显着相关。基于血液的先天免疫谱可能有助于增强痴呆的精准医学方法，有助于识别和监测治疗靶点，并为候选免疫疗法对患者进行分层。