Importantly, the natural Abeta oligomer solution derived from 7PA2 cells used in this and other studies contains Abeta oligomer species similar to those found in AD brain tissue, which when injected into rat brains also impair memory. It is therefore conceivable that injection of 7PA2 derived natural Abeta oligomers into the mouse brain recapitulates a causal factor responsible for memory loss in AD patients, and that the mechanism responsible for Abeta oligomer impaired contextual fear conditioning also contributes to AD associated memory loss. In summary, we found an acute impairing effect of natural Abeta oligomers on contextual fear memory in mice. This finding is in agreement with natural Abeta oligomer induced memory impairments found in previous studies that used rats. Our data show, to our knowledge, for the first time that natural Abeta oligomers can also impair memory in mice. Our study thereby paves the way for using genetic mouse models to study the underlying mechanisms by which natural Abeta oligomers impair memory. This is also, to our knowledge, the first time that an effect of natural Abeta oligomers on fear conditioning is reported.

Since fear conditioning requires only a single learning trial, it is highly suitable for dissecting the different stages of memory, Compound Library allowing to test the contribution of each memory stage to AD associated memory loss. We propose that natural Abeta oligomer impaired fear conditioning can be used to test potential mechanisms and treatments of AD associated memory loss. During early stages of AD, and possibly prevent or delay the progress of AD. Brain tumors are considered amongst the most refractory malignancies. Although several therapies have been developed to improve outcomes in such patients, benefits have been relatively modest. Glioblastoma is the most malignant type of brain tumor and constitutes about 23% of all primary brain tumors. Multimodal treatment including surgery, radiation, and chemotherapy are used but outcomes remain limited. As tumors need oxygen and substrates for growth, they express growth factors stimulating endothelial cell proliferation and capillary sprouting; or angiogenesis. Vascular Endothelial Growth Factor which initiates the endothelial proliferation is a prime mover in this process. Bevacizumab is a humanized monoclonal antibody which sequesters the ligands VEGF-A and -B inhibiting angiogenesis. Bevacizumab has received accelerated approval from the US FDA for the treatment of refractory GBM. A problem with current therapies is that their impact on a particular patient may not be known ahead of time, not to mention the significant costs. As such, after several months of treatment, the treatment results may not be satisfactory.

A predictive model of the tumor response to treatment is thus very helpful to the physicians and patients as it allows them to select the most effective option. Mardor, et al. addressed this problem using two parameters of diffusion weighted imaging in pre-treatment images and showed that these parameters were correlated with the response, defined as relative change in the tumor size. Bezabeh, et al. used several parameters of MR spectroscopy, such as elevation of choline resonance, to predict the response of head and neck cancer to radiation therapy.