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2022 Alzheimer's Association Research Grant (AARG)

Role of synaptic miRNA and astrocyte miRNA delivery in Alzheimer’s disease

Can gene changes in brain structures that help nerve cells communicate lead to Alzheimer’s?

Olivia Belbin, Ph.D.
Institut de recerca de l'hospital de la Santa Creu i Sant Pau
Barcelona, Spain


Research suggests that brain changes associated with Alzheimer’s can occur decades before outward symptoms appear. These brain changes include damage to synapses – the specialized structures nerve cells use to send signals to one another and communicate. Studies show that damage and loss of synapses may be one of the early brain changes observed in Alzheimer’s. However, the mechanism linking synaptic damage and Alzheimer’s remains unclear.

In initial research with human brain tissue, Dr. Olivia Belbin and colleagues found that certain types of microRNAs (miRNAs) were found in synapses. MiRNAs are small molecules that help determine what genes are turned “off” and “on.” Previous studies have shown that problems with miRNAs may lead to the synaptic damage that contributes to memory loss and other hallmark changes of dementia. Scientists have also found dementia-related miRNAs in extracellular vesicles (bubble-like brain structures that are released by cells and carry molecules to other parts of the brain). A particular type of extracellular  vesicle, known as astrocyte-derived extracellular vesicles (ADEVs), are released by astrocytes (a type of support cell in the brain). These ADEVs may carry dysfunctional miRNA to synapses of nerve cells and promote synaptic damage.

Research Plan

Dr. Belbin and colleagues will analyze brain tissue from 10 individuals who had Alzheimer’s and 10 individuals who did not. They will also look at blood samples from 45 individuals with Alzheimer’s, mild cognitive impairment (MCI, a condition of subtle memory loss that may precede Alzheimer’s), or no cognitive impairment.  Using the tissue samples, the researchers will identify miRNA related to synapses in brain regions linked to Alzheimer’s. They will then examine different miRNAs in the Alzheimer’s brain tissue to study how the miRNAs may be linked to synapse loss and other brain features of dementia.
Next, Dr. Belbin’s team will explore the role of astrocyte-derived extracellular vesicles in transporting impaired miRNA to synapses. For this effort, they will analyze their tissue samples to identify all miRNAs in astrocyte-derived extracellular vesicles within brain areas related to Alzheimer’s. They will also identify miRNAs in astrocyte-derived extracellular vesicles within their blood samples. The investigators will then determine how miRNA delivery becomes altered at different stages of Alzheimer’s, and how these changes impact synaptic health and other dementia-related factors over time.    


Results from Dr. Belbin’s study could shed new light on the mechanisms underlying nerve cell damage in dementia. They could also lead to new strategies for detecting and treating Alzheimer’s at an early stage.

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