Amyloid ß and EAAT2 mediated network hyperexcitability and tau propagation

Background Nerve cells use chemicals known as neurotransmitters to send signals to neighboring nerve cells. A common neurotransmitter in the brain is glutamate. However, too much glutamate may contribute to brain changes seen in Alzheimer's such as the accumulation of beta-amyloid and tau, which form plaques and tangles respectively. Dr. Ana Pereira and colleagues are studying one way the brain can remove extra glutamate through a protein (EAAT2). Dysfunction of EAAT2 has been associated with increases in beta-amyloid plaques and excess nerve cell activity. Additionally, increased nerve cell activity has been shown to stimulate tau secretion. In initial research, Dr. Pereira and colleagues developed genetically engineered mice missing EAAT2 in certain types of brain cells. They found that the mice showed Alzheimer's-like changes, as well as changes in genes linked to inflammation. Based on these and other findings, Dr. Pereira believes that beta-amyloid accumulation decreases EAAT2 activity which contributes to increased nerve cell activity and tau tangles.