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2019 Biomarkers Across Neurodegenerative Diseases Grant (BAND)

Oxylipins and Vascular Cognitive Impairment Across the Neurodegenerations

Can certain components in the blood promote a variety of brain diseases?
 

Walter Swardfager, Ph.D.
Sunnybrook Research Institute
Toronto, Canada



Background

As people age, the blood vessels in their brain can become damaged and this can limit the supply of blood and oxygen to the brain cells. Studies show that such damage can increase their risk for Alzheimer’s, Parkinson’s disease and other dementias. Though scientists remain unclear exactly how damage to blood vessels and dementia are linked, recent studies have found that  fats called oxylipins, found in blood, may be involved. Oxylipins normally help promote the health of small blood vessels and reduce inflammation. But when oxylipin levels become abnormal, it may make blood vessels more vulnerable to damage and reduced brain cell function.
 
In preliminary research, Dr. Walter Swardfager, and colleagues found that people with abnormal oxylipin levels also had vascular cognitive impairment (VCI), a disorder involving damage to the brain’s white matter (the “wiring system” through which brain cells communicate) and a loss of  certain cognitive functions. The combination of high oxylipins and VCI was seen in people both with and without Alzheimer’s. Based on these findings, Dr. Walter Swardfager suggests that oxylipin-related damage may precede the development of Alzheimer’s. In addition, other recent studies found that abnormal oxylipin function may also promote the development of Parkinson’s disease.
 

Research Plan

Dr. Swardfager and colleagues will conduct a larger study to clarify the contribution of oxylipins to the development of Alzheimer’s, Parkinson’s disease and other forms of brain diseases. Using the Ontario Neurodegenerative Disease Research Initiative and the Alzheimer’s Disease Metabolomics Consortium, the researchers will collect blood samples, brain scan data, and cognitive test results from 955 participants with either Alzheimer’s or Parkinson’s. The researchers will measure levels of 72 different oxylipins content in the participants’ blood, using a sophisticated test. Next, Dr. Swardfager and his team will determine how oxylipin content is linked to (1) blood vessel damage in the brain, (2) the risk of Alzheimer’s or Parkinson’s disease, and (3) the severity and progression of Alzheimer’s or Parkinson’s.  The researchers will compare oxylipins from the participants in these studies to that of cognitively unimpaired individuals as well as those who have a history of stroke.
 

Impact

The study results could clarify our understanding of how blood vessel damage impacts brain dysfunction and dementia. The results could also help identify the biological mechanisms by which damage to the blood vessels may contribute to brain diseases

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