2021 Alzheimer's Association Research Fellowship (AARF)

Novel MicroRNAs to Treat Dementia-Related Memory Impairment in a Rat Model

How might stroke treatment impact the development of cognitive decline in Alzheimer’s and other dementia?

Dayalan Sampath, Ph.D.
Texas A&M University Health Science Center
College Station, TX - United States

Background

Past research suggests that stroke increase a person’s risk of developing dementia in later life. Studies have found that blood vessel (vascular) damage in the brain could lead to deficits in brain function and cognition and contribute to the onset of dementia. After a stroke, which blocks blood flow in the brain, dementia can sometimes occur suddenly or gradually, leading to changes in cognitive skills. 

Vascular dementia is a decline in cognitive skills caused by conditions that block or reduce blood flow to various regions of the brain, depriving them of oxygen and nutrients. Research suggests that individuals who have had a stroke may also be at increased risk for vascular dementia and also for Alzheimer’s. Some researchers believe that prevention of recurrent strokes and prompt treatment of stroke may reduce vascular contributors to this risk. 

An emerging therapeutic in stroke treatment is the use of microRNAs (miRNAs), which are small molecules that affect genes being turned on or off and therefore can impact many important biological processes. In previous studies in middle-aged female rats, Dr. Dayalan Sampath and colleagues showed that miRNA treatment may reduce inflammation following stroke and improve cognitive symptoms.

Research Plan

Based on their past results, Dr. Sampath and team will test miRNA treatment after stroke in male cognitively unimpaired rats and in genetically engineered Alzheimer’s-like rats. The researchers believe that reducing cell damage after stroke will benefit long-term consequences, including reducing cognitive impairment. 

The researchers will study how miRNA treatment impact the development of cognitive impairment after stroke and evaluate the interaction of stroke and Alzheimer’s-related changes in brain biology on cognitive impairment. The researchers will compare the performance of the rats on a series of behavioral and cognitive tests before and after stroke. In addition, the research team will evaluate the impact of stroke and miRNA treatment on markers of inflammation in the blood at several time points. Finally, Dr. Sampath and colleagues will evaluate changes in the rats’ brains at 100 days post-stroke.
 

Impact

This project may help identify novel therapeutic approaches for reducing the risk of developing Alzheimer’s after a stroke. In addition, the results may be applicable to individuals with other types of dementia, such as vascular dementia.