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Does beta-amyloid contribute to increased nerve cell activity in Alzheimer's?
Ana Pereira, M.D.
Icahn School of Medicine at Mount Sinai
New York, NY - United States
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.
Research Plan
To study the role of EAAT2 in the spread of tau, the team will inject tau proteins from individuals who had Alzheimer’s into the brains of genetically engineered mice with elevated and reduced levels of EAAT2. They will study whether increased glutamate activity contributes to the spreading of tau into other regions of the brain. Additionally, they will create a genetically engineered Alzheimer-like mouse model which develops beta-amyloid and has low EAAT2 activity. They will then treat the mice with a drug to stop production of beta-amyloid to determine whether it impacts nerve cell activity.
Impact
The study findings could provide insights into how nerve activity could impact tau spread in Alzheimer’s. If successful, the results could also reveal potential therapeutic targets for Alzheimer’s treatments.
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