Search

Thriving literature underlines white blood cell involvement in the inflammatory processes of Alzheimer's Disease (AD). Among leukocytes, lymphocytes have been considered sentinels of neuroinflammation for years, but recent findings highlighted the pivotal role of neutrophils. Since neutrophils that infiltrate the brain through the brain vascular vessels may affect the immune function of microglia in the brain, a close investigation of the interaction between these cells is important in understanding neuroinflammatory phenomena and the immunological aftermaths that follow. This study aimed to observe how peripheral leukocyte features change at different stages of AD to identify potential molecular markers when the first features of pathological neurodegeneration arise. For this purpose, the examined patients were divided into Mild Cognitive Impairment (MCI) and severely impaired patients (DAT) based on their Cognitive Dementia Rating (CDR). The evaluation of the neutrophil-to-lymphocytes ratio and the morphology and function of leukocytes showed a close relationship between the ultrastructural and the molecular features in AD progression and suggested putative markers for the early stages of the disease. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia, but the pathogenetic factors are not yet well known, and the relationships between brain and systemic biochemical derangements and disease onset and progression are unclear. We aim to focus on blood biomarkers for an accurate prognosis of the disease. We used a dataset characterized by longitudinal findings collected over the past 10 years from 90 AD patients. The dataset included 277 observations (both clinical and biochemical ones, encompassing blood analytes encompassing routine profiles for different organs, together with immunoinflammatory and oxidative markers). Subjects were grouped into four severity classes according to the Clinical Dementia Rating (CDR) Scale: mild (CDR = 0.5 and CDR = 1), moderate (CDR = 2), severe (CDR = 3) and very severe (CDR = 4 and CDR = 5). Statistical models were used for the identification of potential blood markers of AD progression. Moreover, we employed the Pathfinder tool of the Reactome database to investigate the biological pathways in which the analytes of interest could be involved. Statistical results reveal an inverse significant relation between four analytes (high-density cholesterol, total cholesterol, iron and ferritin) with AD severity. In addition, the Reactome database suggests that such analytes could be involved in pathways that are altered in AD progression. Indeed, the identified blood markers include molecules that reflect the heterogeneous pathogenetic mechanisms of AD. The combination of such blood analytes might be an early indicator of AD progression and constitute useful therapeutic targets. [ABSTRACT FROM AUTHOR]