2024 Alzheimer's Association Research Grant (AARG)
Validation of MAO-B as a PET Biomarker of Reactive Astrogliosis in ADRD
Could a certain molecule indicating when brain support cells are overwhelmed, serve as a marker of Alzheimer’s or related dementia?
Alberto Serrano-Pozo, M.D., Ph.D.
Massachusetts General Hospital
Charlestown, MA - United States
Background
In Alzheimer’s, the proteins beta-amyloid and tau accumulate to form plaques and tangles respectively, two hallmark brain changes observed in the disease. Beta-amyloid plaques may hinder nerve cell communication in the brain and may contribute to brain cell death, loss of memory and other cognitive function. Astrocytes are the most numerous cell type in the brain and play an important role in supporting nerve cell function. However, in Alzheimer’s and related dementia, astrocytes can proliferate and become activated or “reactive” in a process called astrogliosis. Astrogliosis can contribute to the disease by releasing molecules that can damage synapses, specialized structures that nerve cells use to send signals to one another.
Recent research indicated that positron emission tomography (PET) imaging can detect astrogliosis in individuals with certain types of Alzheimer’s by using molecules that highlight a protein called monoamine oxidase-B (MAO-B). More research is needed to determine whether MAO-B could be used as an indicator of certain types of Alzheimer’s disease or related dementias.
Research Plan
Dr. Alberto Serrano-Pozo and colleagues will study MAO-B in the brains of individuals with Alzheimer's and related dementias. They will utilize brain tissue samples from the Massachusetts Alzheimer’s Disease Research Center (MADRC) Neuropathology Core brain bank to determine what cell types have MAO-B, how protein clumps impact MAO-B levels, and the amount and activity level of MAO-B within the cells. They will also measure astrogliosis in these samples. The research team will compare these measures to information about each person’s age, symptoms, and markers of cognitive decline.
Additionally, the research team will test whether two molecules that could be used for PET imaging, called DED and SMBT-1, will mainly stick to reactive astrocytes. They will test the molecules in brain samples from the MADRC Neuropathology Core brain bank.
Moreover, they will determine where MOA-B is active inside reactive astrocytes and certain nerve cells that are implicated in Alzheimer’s and related dementias. They will use brain samples to conduct super-resolution microscopy of MOA-B and other molecules inside these cells.
Impact
Results from this study could shed new light on the mechanisms underlying Alzheimer’s disease progression. They could also promote the development of new ways to detect Alzheimer’s in its early stages.