Background: The intracerebroventricular injection of beta-amyloid (A beta) in mice allows the investigation of acute effects on cognitive function and cellular pathology. The aim of this investigation was to further characterize the time course of A beta-induced cognitive and behavioural changes and to detect potential molecular mechanisms. Methods: Cannulas were implanted in the lateral cerebral ventricle. 14 days after surgery the mice were injected with A beta 1-42 or phosphate buffered saline (PBS). Starting 2, 4 or 8 (PBS only 4) days after injection we evaluated cognitive and behavioural performance using the modified hole board test (mHBT). We determined tumour-necrosis factor alpha (TNF alpha) and caspase 3 by western blotting, on days 10, 12 and 16. Data were analysed using general linear modelling, Kruskall-Wallis and Mann-Whitney-U test. Results: A beta induced a decline in cognitive performance represented as an increased total number of wrong choices during the testing period from day 2-15 (p < 0.05). Behavioural parameters were comparable between mice treated with A beta and PBS. There was no difference regarding TNF alpha levels between the groups. Compared to day 16 Caspase 3 levels were increased on day 10 (p = 0.004). Conclusions: Application of A beta in the lateral ventricle of mice is associated with cognitive impairment of declarative memory in the mHBT. There is no interference caused by altered behaviour. Therefore, it represents a valid model for acute A beta-mediated neurotoxic effects. Although the exact mechanisms remain unclear, changes in levels of Caspase 3 suggest apoptosis as an important factor for the development of cognitive dysfunction.(C) 2017 Elsevier B.V. All rights