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2021 Alzheimer's Association Research Grant (AARG)

Deciphering Human Astrocyte-Neuron Crosstalk in Alzheimer's disease

How do support cells in the brain impact brain changes observed in Alzheimer’s?

Amaia Arranz, Ph.D.
Achucarro Basque Center for Neuroscience
Leioa, Spain


Astrocytes, commonly known as “support cells,” are the most numerous cell type in the brain where they play an important role in supporting nerve cell function. In Alzheimer’s,  certain astrocytes become “reactive” and can release molecules that can damage synapses. Synapses are specialized structures that nerve cells use to communicate with one another. 

Previous studies have used genetically engineered Alzheimer’s-like mouse models to understand how reactive astrocytes may be associated with brain changes observed in Alzheimer’s. The studies have found that reactive astrocytes may undergo changes in their structure and function at early stages of Alzheimer’s and that these changes may increase with the progression of Alzheimer’s. These findings suggest that astrocytes may impact brain changes observed in Alzheimer’s-like mice. Dr. Amaia Arranz believes that human astrocytes may become reactive during Alzheimer’s and may lose their ability to protect nerve cells which could be associated with nerve cell damage and death.

Research Plan

Dr. Arranz and colleagues will use a specialized type of stem cell collected from adult human tissue called iPSCs (induced Pluripotent Stem Cells). iPSCs can be programmed to grow into any type of cell in the human body including  nerve cells and astrocytes. In a laboratory dish, the researchers will expose these cells to beta-amyloid and proteins associated with inflammation (individuals with Alzheimer’s have increased levels of brain inflammation). The researchers will then study the potential changes in astrocyte shape and function. To understand the reactive states that astrocytes may enter in Alzheimer’s, Dr. Arranz’s team will also measure levels of different proteins and RNA (when cells activate a gene, they produce a small piece of corresponding genetic material, called ribonucleic acid - RNA) found in the astrocytes. 

Finally, the researchers will transplant nerve cells and astrocytes generated from iPSCs into genetically engineered Alzheimer’s-like mice. Dr. Arranz’s team will then study how different astrocyte reactive states may impact nerve cell damage and death. Further, they will validate the findings using brain tissue samples - from individuals with Alzheimer’s - in a laboratory dish.


The study results may help understand the impact of astrocytes in brain changes observed in Alzheimer’s. If successful, the findings may lead to a potential therapeutic target to tackle Alzheimer’s. 

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