Altered peripheral immune cell profiles in Tg-SwDI mice compared with wild-type controls.

Abstract

Sporadic Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disorder characterized by numerous pathological processes occurring both in the brain and in the periphery, including chronic local or systemic inflammation, cerebrovascular impairment, oxidative stress, mitochondrial dysfunction, amyloidosis, synaptic and neuronal network dysfunction, metabolic syndrome, and disrupted cell signaling pathways. Although these mechanisms have been extensively studied, the contribution of the peripheral immune system to the etiology and progression of AD remains poorly understood. Emerging evidence suggests that pathological events in the brain, such as amyloid and phosphorylated tau accumulation, neurodegeneration, and neuroinflammation, may trigger systemic immune responses that alter the distribution and function of peripheral immune cells. However, available findings remain inconsistent. In the present study, we examined age-dependent alterations in peripheral blood immune cell populations in Tg-SwDI mice, a transgenic model of AD. We documented for the first time that transgenic mice exhibited increased proportions of neutrophils and an elevated neutrophil-to-lymphocyte ratio (NLR), along with reduced percentages of T lymphocytes compared with wild-type controls. Furthermore, significant differences in T-cell subpopulations were observed between Tg-SwDI and wild-type animals. Our findings are partially consistent with reported clinical observations in patients with AD. Because no single transgenic mouse model fully recapitulates the complex pathology of AD, and many therapeutic approaches successful in preclinical models have failed in clinical trials, a detailed characterization of disease-related alterations in each model is essential for selecting the most appropriate model to investigate specific mechanisms or therapeutic approaches.