APOE and Cognitive impairment: Delivery of thrombin directly into the brain by intracerebral injection causes significant neuropathology, such as enlargement of cerebral ventricles, an increased number of TUNEL-positive cells, astrogliosis, and an increase in the immunoreactivity for phosphorylated neurofilament and apolipoprotein-E (ApoE) fragments, as well as cognitive impairments including deficits in reference memory and an increase in task latency (Mhatre et al., 2004).