| Abstract [eng] |
Alzheimer's disease (AD) is a widely prevalent age-related neurodegenerative disorder, causing impair-ments in memory and executive cognitive functions. With the rising global incidence and the absence of effective disease-modifying therapies, there is an urgent need to explore alternative therapeutic targets at the molecular level. To develop rational and effective treatments for Alzheimer's disease, it is essential to understand the mechanisms underlying its pathogenesis and progression. AD is characterized by a triad of pathobiological markers in the brain: beta-amyloid accumulation, neurofibrillary tangles composed of phosphorylated tau protein, and neuroinflammation. The latter is currently considered one of the main culprits in synaptic dysfunction associated with cognitive impairment. Moreover, Alzheimer's risk factors such as aging, obesity, diabetes mellitus, and chronic infections are associated with peripheral inflamma-tion. The role of systemic inflammation in Alzheimer's pathogenesis and its connection to neuroinflamma-tion may represent a critical area in the search for new therapeutic approaches. The aim of this study was to perform an extensive literature review to evaluate the interaction between systemic inflammation and neuroinflammation and their significance in AD pathogenesis. Scientific article databases such as PubMed and Scopus were searched using keywords: "Alzheimers disease," "AD," "Alzheimer's disea-se," "Systemic inflammation," "Neuroinflammation," and "Peripheral inflammation." Current literature indicates that neuroinflammation plays a significant role in Alzheimer's pathogenesis. Neuroinflammation is induced by beta-amyloid accumulation and products of neuronal damage. Activated microglia play a crucial role during neuroinflammation, producing inflammatory cytokines, complement components, and other excitotoxic substances, causing neuronal damage. Peripheral inflammation also contributes to the pathogenesis of Alzheimer's disease. Chronic infections, such as periodontitis, induce systemic inflamma-tion, increasing blood-brain barrier permeability and activating microglia. Gut microbiota dysbiosis causes peripheral intestinal inflammation, releasing lipopolysaccharides into circulation, which further promotes cognitive decline, beta-amyloid, and phosphorylated tau pathology in the brain. Additionally, obesity in-duced by high-calorie diets is associated with low-grade systemic inflammation caused by hormones, inf-lammatory cytokines, and chemokines produced in the liver and adipose tissue, resulting in brain atrophy, microgliosis, and memory impairments. With aging, disruption of peripheral immune balance manifests as immune cell senescence, inflammatory activation, and infiltration into the brain, contributing to neuroinf-lammation and modulating beta-amyloid phagocytosis. Acute inflammatory conditions, such as trauma and acute infections, also promote Alzheimer's pathology. Trauma induces neuroinflammation, and in-fection-causing microorganisms influence the brain either directly or indirectly through produced substan-ces. Thus, both acute and chronic peripheral inflammation accelerate the development of Alzheimer's pat-hology and neuroinflammation, highlighting a significant area for further research aimed at identifying new therapeutic targets for Alzheimer's disease. |
