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2023 Alzheimer's Association Research Grant (AARG)

Exploring the Human Microglial Secretome in Alzheimer’s Disease

How might the proteins secreted by the brain’s immune cells contribute to inflammation and cell death in Alzheimer’s? 

Renzo Mancuso, Ph.D.
Flanders Institute for Biotechnology (VIB)
Gent, Belgium


Microglia are the primary immune cells of the brain and help maintain the health of nerve cells. Individuals with Alzheimer’s typically experience brain inflammation caused by changes in the immune system, including increased activity of microglia. Overactive microglia can release proteins called cytokines that promote brain inflammation and may lead to nerve cell death. Cytokines may contribute to inflammation and cell death through their effect on the interactions and communications between cells. However, it is not yet known how microglia communicate with other cells in the brain and how this communication between cells is impacted in Alzheimer’s.

Research Plan

Dr. Renzo Mancuso and colleagues will study how the proteins released by microglia (collectively known as its secretome) may contribute to brain inflammation and nerve cell death in Alzheimer’s. 

The researchers will use a special kind of stem cell derived from adult cells called induced pluripotent stem cells (iPSCs). iPSCs can be made to develop into any kind of cell in the body. Dr. Mancuso and colleagues will use iPSCs to create human microglial cells in laboratory dishes. They will engineer these cells using a novel technique called TurboID that will label all the proteins released by the microglia. Then, the team will transplant these microglia into genetically engineered Alzheimer’s-like mice and identify specific inflammatory proteins released by the microglia. 

Next, Dr. Mancuso and colleagues will look for these inflammatory proteins in samples of cerebrospinal fluid (CSF, a biological fluid surrounding the brain and spinal cord) from individuals who had Alzheimer’s and cognitively unimpaired individuals.


If successful, the findings may contribute to the development of new biological markers and therapeutic strategies to address inflammation in Alzheimer’s and other brain diseases.

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