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2021 Alzheimer's Association Research Fellowship (AARF)

Evaluation of Cortical Microinfarcts in Individuals with Down Syndrome

How may small brain tissue deaths be associated with cognitive decline?

Mateus Aranha, Ph.D.
Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau
Barcelona, Spain



Background

Individuals with Down syndrome are at a high risk for developing Alzheimer’s. By the early age of 40, most people 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. In a closely related disease to Alzheimer’s, called cerebral amyloid angiopathy (CAA), beta-amyloid and tau accumulate around the blood vessels that may be associated with problems with blood circulation. Studies show that this could lead to very small areas of tissue death, known as microinfarcts. People with Down syndrome may also be at a high risk for developing CAA. Until recently, microinfarcts could only be detected in brain tissues, but new brain scan technologies may enable their detection in the live brain. 

Research suggests that microinfarcts may be observed in older adults vulnerable to cardiovascular risk factors. However, since microinfarcts may also be observed in those with Alzheimer’s it is not yet known whether microinfarcts may be associated with cardiovascular risk factors or with CAA.

Dr. Mateus Aranha and colleagues aim to use advanced brain scan (magnetic resonance imaging (MRI)) technology to understand microinfarcts in individuals with Down syndrome, who may be less likely to have cardiovascular risk factors.

Research Plan

Dr. Aranha and colleagues will leverage the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI), a study group of adults with Down Syndrome, as well as the Sant Pau Initiative on Neurodegeneration, a study group of individuals with cognitive decline who do not have Down Syndrome. To test for microinfarcts, the researchers will utilize existing MRI datasets from over 400 individuals from the initiatives and gather new advanced MRI data from 10 individuals. Using the scans, Dr. Aranha’s team will test whether the levels of microinfarcts may be associated with age, cognitive scores, genes, brain changes, and other biomarkers associated with Alzheimer’s from the participant blood and cerebrospinal fluid (biological fluid surrounding the brain and spinal cord) samples. Dr. Aranha believes that the levels of microinfarcts may be associated with brain changes observed in Alzheimer’s and cognitive decline. 

Impact

The study results may identify a potential link between microinfarcts and other brain changes. The findings may help us understand whether microinfarcts may be associated with CAA and individuals with Down Syndrome.

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