T‐cell population and PD‐1 expression in Alzheimer’s disease patients do not follow the age trend of normal individuals

Abstract

AbstractBackgroundDestruction of cerebral neurons may relate to atypical immune responses. These intracerebral immune responses were induced by various antigens, such as viral DNA fragments or misfolded proteins. Aging is the major risk factor for Alzheimer’s disease (AD). Throughout the aging process, people experienced repetitive microbial infections and misfolded protein accumulation. But not every individual developed AD during aging. Immune regulation may contribute to determining whether the brain could clean unfavorable misfolded proteins and maintain homeostasis. T cell populations and programmed death 1 (PD‐1) are involved in immune pathology. In our study, we examined T cells and PD‐1 between normal aging and AD individuals to elucidate the role of immune regulation in aging‐related AD.MethodSixteen normal aging individuals (age range between 65‐91 years old) and 16 AD patients (age range 69‐88 years old) participated in this study. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood. Antibodies against T cells and PD‐1 molecules were used to classify PBMC with flow cytometry.Result(1) T cell population is different between normal and AD individualsThe normal aging group had significantly fewer adaptive immune T cells and fewer helper T cells (TH). However, these immune features were not present in AD patients.(2) PD‐1 pattern in PBMC is different between normal and AD individualsNatural killer T (NKT) cells with CD56 (neural cell adhesion molecule) had increased PD‐1 expression with normal aging. But AD patients did not show this trend of regulatory changes. These trends of suppressive phenotypic changes were absent in AD patients.ConclusionOur study demonstrated that the T‐cell population was shrinking progressively with normal aging. Nerve‐adherent NKT cells exhibited a higher inhibitory receptor (PD‐1). These findings suggested that T‐cell immune population tended to be suppressed with normal aging. However, these characteristic transitions of immune cells were not present in AD patients, suggesting that T cells were prone to activate in older AD patients. These distinctive immunomodulatory features of AD might be potential biomarkers of late‐onset AD, and predictive factors for developing AD in normal aging individuals.