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2018 Alzheimer's Association Research Fellowship (AARF)

Noninvasive Biomarker of CSF Production

Can measuring the loss of a fluid that surrounds the brain help diagnose Alzheimer's?

Li Zhao
Children's National Medical Center
Washington D.C., DC - United States


In Alzheimer's, the sticky protein fragment beta-amyloid tends to form harmful clumps in the brain, called plaques. These clumps affect the function of brain cells and are thought to be leading to brain cell death. Research has found that beta-amyloid clumping may occur, in part, because the brain is less able to clear toxic beta-amyloid. Scientists are now examining how this loss of waste-clearing function occurs in Alzheimer's and how it may influence Alzheimer's-related brain changes.

Recent studies have identified cerebrospinal fluid (CSF) -a biofluid that surrounds the brain and spinal cord- as vital to the brain's waste-clearing mechanisms. CSF appears to serve as a "drainage pathway" for beta-amyloid and other unwanted molecules. Studies have also found links between reduced amount of CSF and Alzheimer's. Based on these efforts and their own preliminary research, Dr. Li Zhao and colleagues hypothesize that a network of brain cells, which helps produce CSF, experiences a loss of blood flow in Alzheimer's. This reduced blood flow may affect these specific brain cells' overall health and, in turn, lower CSF production hindering the brain's ability to clear the toxic beta-amyloid.

Research Plan

For their current grant, Dr. Zhao and colleagues will test their idea by employing a sophisticated scanning technique (arterial spin labeling and magnetic resonance imaging) for measuring blood flow and CSF levels in people with and without Alzheimer's. First, the researchers will assess whether their technique can accurately determine how blood flow in the brain region that helps produce CSF affects its production. They will then use the technique to determine whether the blood flow in this special brain region and CSF levels are reduced in people with Alzheimer's compared to cognitively unimpaired individuals.


Dr. Zhao's study could shed new light on how damage to the brain's waste-clearing mechanism may be linked to give rise to Alzheimer's. It could also identify how being able to measure the levels of CSF production as a contributing biology (or a novel biomarker) of Alzheimer's. This work is exploring a new tool to measure noninvasively, these changes as part of an improved Alzheimer's diagnostic tool.

This project is sponsored by the Alzheimer's Association, Colorado Chapter.

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