Aggregation of the beta-amyloid protein (Aβ) is a hallmark of Alzheimer's disease (AD) and is believed to be causally involved in a neurodegenerative cascade. In patients with AD, reduced levels of serum Brain Derived Neurotrophic Factor (BDNF) and cortical 5-HT2A receptor binding has recently been reported but it is unknown how these changes are related to beta-amyloid accumulation. In this study we examined in rats the effect of intrahippocampal injections of aggregated Aβ(1–42) (1 μg/μl) on serum and brain BDNF or 5-HT2A receptor levels. A social recognition test paradigm was used to monitor Aβ(1–42) induced memory impairment. Memory impairment was seen 22 days after injection of Aβ(1–42) in the experimental group and until termination of the experiments. In the Aβ(1–42) injected animals we saw an abolished increase in serum BDNF levels that was accompanied by significant lower BDNF levels in frontal cortex and by an 8.5% reduction in hippocampal 5-HT2A receptor levels. A tendency towards lowered cortical 5-HT2A was also observed. These results indicate that the Aβ(1–42) associated memory deficit is associated with an impaired BDNF regulation, which is reflected in lower cortical BDNF levels, and changes in hippocampal 5-HT2A receptor levels. This suggests that the BDNF and 5-HT2A changes observed in AD are related to the presence of Aβ(1–42) deposits.