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How do changes in blood vessels impact the hallmark brain changes seen in Alzheimer’s?
Carmen Martinez, M.D., Ph.D.
Fundación Instituto de Investigación Marqués de Valdecilla
Cantabria, Spain
Background
The proteins beta-amyloid and tau accumulate to form plaques and tangles respectively, the two hallmark brain changes observed in Alzheimer's. Beta-amyloid can accumulate near brain blood vessels and these accumulations are associated with increased stiffening of the vessels. When vessels are stiffer, it can be difficult for muscle cells in the blood vessels to properly pump blood, possibly restricting blood flow throughout the brain. This process is known as “cerebral amyloid angiopathy” or CAA.
One way that CAA may alter blood flow is through its impact on the blood-brain barrier (BBB), a specialized structure that helps maintain a healthy brain environment by tightly regulating what goes into and out of the brain from circulating blood. Additionally, damage to the white matter (the primary wiring system in the brain where it is used by nerve cells to communicate with one another) is also a brain change that is thought to drive changes to the BBB.
Increasing evidence suggests that damage to the BBB may impact Alzheimer’s and related dementias, but more research is needed to understand the underlying mechanisms.
Research Plan
In the current study, Dr. Lage Martinez and colleagues will study how the BBB changes during aging, and whether those changes are associated with changes in amyloid and tau accumulation, as well as white matter damage. The researchers will recruit individuals from the Study of Memory and Brain Aging, a large population-based project which aims to advance our understanding of healthy brain aging and the early stages of Alzheimer’s and related dementias. The researchers will use data from 250 cognitively unimpaired individuals.
Dr. Lage Martinez and colleagues will first measure amyloid and tau in both the blood and cerebrospinal fluid (or CSF, the biological fluid surrounding the brain and spinal cord) and associate their levels with specific biological markers (biomarkers) of BBB damage. Next, the team will connect the same biomarkers of BBB damage in the blood with changes in white matter, measured by brain scans, for each individual in the study. Lastly, Dr. Lage Martinez and the team will examine the relationship between BBB damage and specialized immune cells in the brain called microglia, which may play an important role in early Alzheimer’s development and progression.
Impact
If successful, results of this project may help us understand how the BBB changes during aging and its impact on the hallmark brain changes seen in Alzheimer’s. This study has the potential to open the door to new pathways for early and accurate detection of these changes.
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