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2018 Alzheimer's Association Research Fellowship (AARF)

Microglia and neuroinflammation: transducers of Aß toxicity in human AD

Does brain inflammation promote the development of Alzheimer’s?

Renzo Mancuso
VIB Center for Brain and Disease Research
Gent, Belgium


Brain inflammation, has long been identified as a key hallmark of Alzheimer’s. Abnormal activation of immune cells called microglia in the brain leads to brain inflammation. In the past, scientists believed that brain inflammation developed in response to other factors in Alzheimer’s, such as brain cell damage and the build-up of toxic beta-amyloid – a hallmark in Alzheimer’s and other unwanted brain proteins. Recent studies, suggest that brain inflammation also contribute directly to the build-up for beta amyloid plaques and other brain changes see in Alzheimer’s.

Research Plan

Dr. Mancuso and colleagues plan to investigate how inflammation is linked to the progression of Alzheimer’s at the earliest stages. For this project, they will use genetically-engineered mouse models engineered to have increased inflammation in their brains to examine whether brain inflammation causes nerve cell damage and brain changes associated with Alzheimer’s and cognitive impairment.
First, Dr. Mancuso will inject human nerve cells into the brains of these mice, in order to examine how these nerve cells respond to an environment engineered to be similar to the inflammation changes seen in Alzheimer’s. The researchers will assess how brain inflammation directly affects the health of these nerve cells. Next, they will use two methods to examine the role of microglia in Alzheimer’s. In the first method, they will block the production of microglia with chemical compounds in mice, to test what effect that has on nerve cell damage.  In the second method, they will inject human microglia into the mouse brain with the goal of developing a new mouse model to help identify how these immune cells may promote inflammation, beta-amyloid build-up and other Alzheimer’s-related brain changes.


The results of this study will shed new light on the role of inflammation in Alzheimer’s and could ultimately lead to novel therapies that prevent or slow the progress of Alzheimer’s.

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