Composition of Peripheral Blood Leukocyte Subsets in Ratswith Different Models of Alzheimer's Disease

Abstract

Background. Systemic inflammation is recognized a sone of the key features of Alzheimer's disease (AD) – a neurodegenerative disorder, which is characterized by cognitive decline with progressive memory loss and affects millions of predominantlyeld erly people. Recent literature data suggest the involvement of periphera limmune cells in the initiation and progression of AD. However, our understanding of the population composition of peripheral blood leukocytes and its contribution to disease progression remains limited. The use of anima lmodels plays an important role in investigating possible mechanisms linking the periphera limmune system to the inflammatory processes underlying neurode generation. The aim of this study was comparative assessment of the composition of leukocyte subsets in rats with AD, induced by intrahippocampa linjection of amyloidbeta (Aβ) 1–40 and Aβ 25–35. Methods. Male Wistar rats were used in the experiments, including intact and sham-operated animals as controls. Disease development was confirmed b y assessing cognitive impairment in the Barnesmaze be havioral test and by the loss of dopaminergic neurons. Hematological parameters were evaluatedat the end of the experiment (day 37 after the disease initiation), including absolute leukocyte count, as well as absolute and relative count of their main subsets: lymphocytes, monocytes, andneutrophils. Rats with AD induced by Aβ 1–40 exhibited granulocytosis (a fivefold increase in absolute granulocyte countin the circulation). Absolute and relative count of lymphocytes In these animals were decreased on average by 2.5 times, monocyte count – on average by 3 times as compared to those in intactand sham-operated rats.In rats with Αβ 25–35-induced AD, leukocytosis with slightly decreased lymphocyte proportion, increase in monocyte count twice at average and unchanged neutrophil countwere revealed. Results. Therefore, animalswith AD, inducedby Aβ 1–40, had hematologic markers of systemic inflammation (leukocytosis, granulocytosis, lymphocytopenia, andmonocytopenia). Conclusions. These results suggest that the Aβ 1–40-induced AD model more accurately reproduces the hematologic signs of systemic inflammation observed in patients with this pathology.