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2022 Alzheimer's Association Research Grant (AARG)

Multimodal Assessment of Brain Inflammatory Biomarkers in DS-associated AD

How do biological markers of brain inflammation change in individuals with Down syndrome who develop Alzheimer’s?

Maria Carmona Iragui, MD, Ph.D.
Institut de Recerca de L’hospital de la Santa Creu I Sant Pau
Barcelona, Spain


The immune system is complex and serves to maintain our overall health. In the brain, the immune system helps maintain healthy nerve cells. Microglia are the primary immune cells of the brain, and they play a major role helping to maintain healthy nerve cells. Microglia are also implicated in brain diseases, including Alzheimer’s. Increased activity of microglia can lead to brain inflammation, which can damage nearby nerve cells and is common in individuals with Alzherimer’s

Individuals with Down syndrome are at a high risk for developing Alzheimer’s. By the early age of 40, most individuals with Down syndrome have a build-up of beta-amyloid plaques and tau protein tangles in their brains, both hallmark brain changes observed in Alzheimer’s. These brain changes contribute to the inflammation caused by the microglia.

Several emerging methods allow for detection of early brain changes associated with Alzheimer’s in the blood and cerebrospinal fluid (CSF, the biological fluid surrounding the brain and spinal cord). These methods require measuring specific biological markers, or “biomarkers” (such as the level of beta-amyloid or tau protein). Further, the development of Alzheimer’s-related brain changes begins well before cognitive symptoms appear and therefore, identifying other, novel biomarkers of Alzheimer’s, such as markers of inflammation, could help detect the disease earlier. 

However, the exact mechanism of how inflammation develops in the brains of individuals with Alzheimer’s and Down syndrome, remains unclear.

Research Plan

Dr. Maria Carmona Iragui and colleagues will study biomarkers of brain inflammation in individuals with Down syndrome across stages of Alzheimer’s. Their data will come from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI), which includes a large group of individuals with Down syndrome. The research team will study 92 biomarkers of inflammation in samples of blood and CSF. 

Dr. Iragui and team will study how the biomarkers of inflammation they identify in blood and CSF are associated with traditional biomarkers of Alzheimer’s and cognitive decline. The researchers will also examine which of these biomarkers are associated with brain metabolites (compounds produced when the body breaks down large molecules) that are increased in individuals with Down syndrome and Alzheimer’s.


This project may provide a new understanding of how brain inflammation develops in the earliest stages of dementia. Additionally, the results may guide the development of new biomarkers of Alzheimer’s.

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