IMMUNOHISTOCHEMICAL EVALUATION OF AUTOPHAGY MARKERS IN THE HUMAN HIPPOCAMPUS DURING AGING AND ALZHEIMER'S DISEASE

INTRODUCTION. Autophagy is a key mechanism for the removal of damaged organelles in neurons, and its dysfunction underlies aging and the pathogenesis of many neurodegenerative diseases, including Alzheimer's disease. However, the specific features of the autophagic response in different hippocampal regions that ex-hibit selective vulnerability in Alzheimer's disease remain poorly understood.
OBJECTIVE. The aim of this study was to comprehensively evaluate autophagy markers in neurons of the CA1 and CA2 zones of the human hippocampus during physiological aging and Alzheimer's disease.
MATERIALS AND METHODS. The work was performed on autopsy material from young patients (35-45 years old, n=20), elderly patients without neurodegenerative pathology (>85 years old, n=20), and patients with Alzheimer's disease (Braak stage 3-4, >85 years old, n=15). Markers of ubiquitin, pS65-Ub, TOMM20, SQSTM1/p62, Beclin-1, LC3b, and LAMP2 were determined immunohistochemically, and staining intensity in the neuronal perikarya was assessed.
RESULTS. It was found that, with age, compensatory activation of autophagy markers is absent in the CA1 zone against the background of accumulation of the adapter protein p62, whereas in the CA2 zone, an in-crease in Beclin-1 and LAMP2 is observed with a decrease in the number of mature autophagosomes (LC3b). In Alzheimer's disease, a decrease in the number of initiation complexes containing Beclin-1 and accumula-tion of autophagosomes (LC3b) are observed in both zones; however, in the CA2 zone, a decrease in the amounts of LAMP2 and p62 is additionally recorded, indicating a block in the terminal stages of autophagy.
CONCLUSION. The obtained data indicate pronounced zonal heterogeneity of the autophagic response in the hippocampus both during aging and in Alzheimer's disease. The identified differences in the autophagy pro-cess in the CA1 and CA2 zones confirm the need for a differentiated approach to the selection of targeted drugs for the treatment of neurodegenerative changes.

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