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Relevance. Alzheimer’s disease (AD) is the most cause of disability and dementia, which is the 7th leading cause of death worldwide. Diagnosis of AD includes detection of amyloid plaques and hyperphosphorylated tau protein (pTau) in the brain. However, in recent years the amyloid hypothesis of AD development has been criticized and revised, and a growing pool of data emerges indicating more complex pathogenetic mechanisms leading to neurodegeneration in AD. The aim of our work was to evaluate the presence and distribution of amyloid plaques and pTau fragments in different regions of the cerebral cortex in patients 60 years old with diagnosed dementia and without cognitive impairment, as well as in people 60 years old. Materials and Methods. The amount of β-amyloid and pTau fragments in three groups of patients was measured on IHC stained histological sections in the regions of parahippocampal, temporal, and occipital cortex. Results and Discussion. Amyloid plaques were detected in all patients over 60 years of age (with and without dementia), while in younger individuals 60 years of age they were found in 66% of cases. The largest amyloid-β burden was observed in the occipital cortex. pTau was detected in all cortical areas in the three groups of patients. Also, the amount of pTau was higher in the occipital cortex in patients over 60 years of age both with and without dementia than in the group of people under 60 years of age. Conclusion. Thus, accumulation of pTau occurs earlier than β-amyloid. The amount of pTau was higher in patients over 60 years of age with clinically manifested dementia, while in some regions the amount of amyloid conglomerates is higher in cognitively intact patients. The findings point to much more complex mechanisms of the neurodegenerative diseases development with the formation of amyloid plaques being a consequence rather than cause of the disease.

Relevance . Macrophages are the leading regulatory cell-lineage taking part in reparative processes in mammals, and the liver is no exception. The ratio of monocyte migration, proliferation and death of macrophages during liver regeneration requires further studies. The aim was to quantify the intensity of monocyte migration, cell proliferation and apoptosis of resident liver macrophages after its 70 % resection in a mouse model. Materials and Methods. We performed 70 % liver resection in sexually mature male BalbC mice. Cells of liver monocyte-macrophage system were obtained by magnetic sorting by marker F4/80. The immunophenotype of the isolated cells was further studied by cytofluorimetry, the level of proliferation and cell death, the content of cyclins and P53 was determined by western blot. Results and Discussion . It was found that after partial hepatectomy there is a marked migration of monocytes/macrophages positive for Ly6C and CD11b markers to the liver, the migration process starts already in the first day after the operation. On the same terms there is a rise in proliferative activity of macrophages, established by Ki67 marker, the peak of proliferation - 3 days after partial hepatectomy. A significant increase in the number of dying macrophages was found early after liver resection. Conclusion . The obtained data indicate that liver regeneration in mammals on the model in mice is accompanied by proliferation migration and cell death of macrophages. Taking into account the immunophenotype of macrophages, we can conclude that Ly6C+ blood monocytes migrate to the liver, and resident macrophages participate in proliferation. The obtained data confirm the universality of the course of reparative processes in mammals.

Abstract Background In many clinical cases of extensive liver resection (e.g. due to malignancy), the residual portion is too small to maintain the body homeostasis. The resulting acute liver failure is associated with the compensatory growth inhibition, which is a typical manifestation of the ‘small for size’ liver syndrome. The study investigates possible causes of the delayed onset of hepatocyte proliferation after subtotal hepatectomy (80% liver resection) in rats. Results The data indicate that the growth inhibition correlates with delayed upregulation of the Tnf gene expression and low content of the corresponding Tnfα protein within the residual hepatic tissue. Considering the involvement of Tnf/Tnfα, the observed growth inhibition may be related to particular properties of liver macrophages – the resident Kupffer cells with CD68+CX1CR3−CD11b− phenotype. Conclusions The delayed onset of hepatocyte proliferation correlates with low levels of Tnfα in the residual hepatic tissue. The observed growth inhibition possibly reflects specific composition of macrophage population of the liver. It is entirely composed of embryonically-derived Kupffer cells, which express the ‘proregeneratory’ M2 macrophage-specific marker CD206 in the course of regeneration.