Therapeutic potential of HSP70 in correcting cognitive deficits and its effect on beta-amyloid formation in Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by the progressive accumulation of beta-amyloid and impaired cognitive function. Existing treatments are not effective enough, it’s necessary to search for new therapeutic strategies targeting key pathogenetic mechanisms.

The aim. To investigate the therapeutic potential of intracellular and extracellular forms of heat shock protein HSP70 for correcting cognitive deficits and reducing amyloid load in AD.

Materials and methods. The study was performed on APPswe/PS1dE9/Blg transgenic mice, modeling AD, and lines created on their basis expressing intracellular (Tg_h) or extracellular (Tg_h_mod) forms of human HSP70. Behavioral tests were used to assess cognitive functions: Open Field, Novel Object Recognition, Y-maze, Barnes Maze. Amyloid load was assessed by histological method.

Results. The extracellular form of HSP70 (Tg_h_mod) significantly reduced amyloid load by 37% (p = 0.0033) and demonstrated marked cognitive improvement — by 40–45% in the Y-maze and Barnes Maze tests, whereas the intracellular form (Tg_h) reduced amyloidosis by 23.6% (p = 0.0273) but did not show significant memory recovery. The results indicate that the neuroprotective effect of extracellular HSP70 is likely mediated not only by chaperone activity but also by additional mechanisms critical for synaptic function.

Conclusion. A comparative study of the effectiveness of intracellular and extracellular forms of HSP70 in correcting both molecular and behavioral disorders in an AD model was conducted for the first time. It was found that the modified form of HSP70 has therapeutic potential. HSP70, especially its extracellular form, is a promising target for the development of AD therapy, providing a comprehensive effect on amyloid pathology and cognitive functions.

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