Laboratory of Emotions Neurobiology, Nencki Institute of Experimental Biology PAS.
Laboratory of Emotions Neurobiology, Nencki Institute of Experimental Biology PAS;
Acta Neurobiol Exp (Wars). 2023;83(2):127-139. doi: 10.55782/ane-2023-012.
APOE‑ε4 genotype (apolipoprotein E, epsilon 4) is the strongest genetic risk factor for Alzheimer's disease (AD). Despite years of research, it is still not known how it contributes to dementia development. APOE has been implicated in many AD pathology mechanisms, like Aβ clearance, brain metabolism, changes within microglia and other glial functions and inflammatory processes. In fact, immunological/inflammatory processes are recently discussed as an important factor in Alzheimer's development and granulocyte profiles changes are reported in patients. However, the exact link between the immune system and risk‑genes is unknown. In particular, it is not known whether and how they interact throughout the lifetime, before the disease onset. The aim of the study was to investigate the relationship between granulocyte count and the APOE/PICALM genes in healthy individuals with an increased genetic risk of AD. An exploratory analysis regarding other blood cells was also conducted. Blood samples were collected from 77 healthy middle‑aged (50-63 years old) participants, who were also asked to complete a health and life‑style questionnaires. Groups with different AD risk‑genes were compared. Differences in granulocyte profiles were found in healthy carriers of AD risk‑genes who had slightly elevated eosinophil levels as compared to non-risk carriers. An exploratory analysis showed some alteration in mean corpuscular hemoglobin content and concentration (MCH/MCHC) levels between risk‑carriers subgroups and non-risk carriers. No other differences in blood count or lipoprotein profile were found between healthy APOE/PICALM risk‑carriers and non-risk carriers. Longitudinal studies will reveal if and how those changes contribute to the development of AD pathology.
载脂蛋白 E-ε4 基因型（载脂蛋白 E，ε4）是阿尔茨海默病（AD）最强的遗传风险因素。尽管经过多年研究，但其如何导致痴呆的发展仍不清楚。APOE 已被牵连到许多 AD 病理机制中，如 Aβ 清除、脑代谢、小胶质细胞内的变化和其他神经胶质功能及炎症过程。事实上，免疫/炎症过程最近被认为是 AD 发展的一个重要因素，患者的粒细胞谱发生变化。然而，免疫系统与风险基因之间的确切联系尚不清楚。特别是，尚不清楚它们在疾病发作之前是否以及如何在整个生命周期中相互作用。本研究旨在探讨健康个体中粒细胞计数与 APOE/PICALM 基因之间的关系，这些个体具有 AD 的遗传高风险。还对其他血细胞进行了探索性分析。从 77 名健康中年（50-63 岁）参与者中采集了血液样本，他们还被要求完成健康和生活方式问卷。比较了具有不同 AD 风险基因的组。与非风险携带者相比，具有 AD 风险基因的健康携带者的嗜酸性粒细胞水平略有升高，其粒细胞谱存在差异。探索性分析显示，风险携带者亚组与非风险携带者之间的平均红细胞血红蛋白含量和浓度（MCH/MCHC）水平存在一些变化。在健康的 APOE/PICALM 风险携带者和非风险携带者之间，未发现血细胞计数或脂蛋白谱的其他差异。纵向研究将揭示这些变化是否以及如何导致 AD 病理的发展。
