Alzheimer's disease (AD) is one of the most significant neurodegenerative diseases, and its effective treatment remains a challenge. Dehydroepiandrosterone (DHEA) is an androgen molecule, which in vitro protects against amyloid-ß (Aß) toxicity, and so might potentially improve cognitive functions. As steroid might influence wide range of processes both short (via membrane receptors) and long term (via intracellular receptors) we can expect beneficial effect already after one injection.Six months old male 3xTg-AD mice were treated intraperitoneally with DHEAS (a water-soluble sulphate salt of DHEA, 10 mg/10ml/kg) and compared to vehicle treatment. Behavioural tests (Y-maze and social discrimination) were performed 30 minutes after the injection, and after 24/48 hours the animals were transcardially perfused. We performed immunohistochemistry on 30 μm thick brain sections for acetylcholinesterase (AChE, cholinergic fibre density) amyloid-β accumulation, and pTau neurofibrillary tangles.In previous studies we observed that the 3xTg-AD animals exhibited increased anxiety and cognitive disorders. However, DHEAS treatment 30 min before the tests was not able to improve the behavioural symptoms. Nevertheless, amyloid plaques and neurofibrillary tangles appeared in the brains of these mice, and we also detected reduced cholinergic fibre density in the sensory cortex. The DHEAS treatment significantly reduced the number of amyloid plaques in some areas.In conclusion, our findings support the potential of DHEAS as a protective agent for nerve cells, suggesting its usefulness as a novel therapeutic option for neurodegenerative diseases, including AD. A single injection might be effective, however, longer time seems to be needed for development of the effect.