Altered granulocyte count and erythrocyte measures in middle‑aged, healthy carriers of APOE and PICALM risk genes for Alzheimer’s disease

Abstract

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 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.