2023 Alzheimer's Association Clinician Scientist Fellowship (AACSF)
Imaging of Astrogliosis and Functional Connectivity in Alzheimer's Disease
How may dysfunctional “helper” cells in the brain promote changes in nerve cell communication that lead to Alzheimer’s?
Boris-Stephan Rauchmann, M.D.
LMU University Hospital Munich
Munich, Germany
Background
Individuals with early-stage Alzheimer’s experience brain inflammation that may lead to other disease-related brain changes, such as the clumping of beta-amyloid protein and the eventual loss of memory and other cognitive functions. According to research, these changes may be linked to changes in “functional connectivity” – or the way nerve cells in certain brain regions communicate with each other. Studies also indicate that functional connectivity changes may be related to “astrogliosis,” or the abnormal activity of “helper” cells in the brain called astrocytes. Scientists, however, are uncertain exactly how astrogliosis may alter functional connectivity in ways that affect Alzheimer’s progression.
Research Plan
Dr. Boris-Stephan Rauchmann and colleagues will analyze the links between astrocytes and brain cell connectivity in Alzheimer’s. They will use positron emission tomography (PET) and magnetic resonance imaging (MRI) brain scan methods to study the brains of 60 human participants – 20 with mild Alzheimer’s, 20 with mild cognitive impairment (or MCI, a condition of subtle cognitive loss that may precede Alzheimer’s) and 20 with no cognitive impairment. First, the researchers will measure and compare astrogliosis levels in the groups. They will then examine how astrogliosis in certain parts of the brain may be related to functional connectivity changes in those regions – and how such relationships differ in individuals with and without Alzheimer’s. Lastly, Dr. Rauchmann’s team will explore how abnormal activity of immune cells called microglia (or microgliosis, another brain change linked to inflammation in Alzheimer’s) may interact with astrogliosis to promote dementia-related connectivity changes.
Impact
Results from this study could shed new light on the mechanisms underlying Alzheimer’s disease progression. They could also promote the development of novel anti-inflammatory disease treatments.