Neurologist Mike Harrington of Pasadena, California's Huntington Medical Research Institutes argues that soon we may be able to detect brain disease before symptoms even begin. The secret is in the cerebrospinal fluid, the clear liquid that cushions our brain and spinal cord.
As guest editor for the January 2006 issue of the respected medical journal Disease Markers (Volume 22, Issues 1-2), published by IOS Press, which was themed to the study of neural markers, Harrington edited the issue and co-authored three of the articles himself. He worked with HMRI biochemist Alfred Fonteh and several other scientists.
"Changes in lipids (e.g. cholesterol) and proteins in our cerebrospinal fluid may be linked to various brain conditions," Harrington says. "Conditions could include any change in normal brain, such as in development, or in diseases such as migraine, Parkinson's Disease, schizophrenia, Alzheimer's Disease, depression, multiple sclerosis and some forms of stroke.
A marker is a molecule in the body that's involved in a disease, for example in the metabolism of a cancer cell. The marker points to a disease like a glove dropped by a cat burglar.
"We suspect that a problem in processing cholesterol in the brain may be at the root of Alzheimer's disease," Harrington adds. (A surprise to most people, the brain contains 25 percent of the body's cholesterol.) Studying the cholesterol in the brain may help provide an earlier diagnosis.
Harrington is known for his discovery of a marker for mad cow disease which advanced the worldwide study of the brain-wasting condition. His current research into migraine markers at HMRI is entering its fourth year of funding from the National Institutes of Health in Washington.
Harrington's first article in the journal was a review of 131 articles written by scientists who have studied disease markers in spinal fluid. In the past 27 years, there's been a 50-fold increase in the number of proteins identified in the cerebrospinal fluid – now a total of about 700. However, Harrington says, "The task ahead is enormous. There may be hundreds of thousands of molecules or their fragments that could serve as disease markers if we knew what they were and what they do in the spinal fluid."
To get where they need to be in their knowledge of proteins, Harrington calls on clinicians who see patients and researchers who mostly study animals to share their knowledge.
"Currently there's a disagreement between the two groups over what constitutes a breach of the blood-brain barrier," Harrington says. "Clinicians believe that the barrier is compromised when a few stray molecules are present. Research physiologists have shown for 15 years that's incorrect."
"We see a mismatch between the two disciplines," Harrington says. "Their separate stores of data, if combined, could provide significant insights into a variety of brain disorders."