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Researchers at Loma Linda University School of Medicine and George Mason University find promising biomarker source in early detection of Alzheimer’s

Matthew Scrag, a graduate student in the Loma Linda University School of Medicine (LLUSM), and Wolff Kirsch, MD, professor of neurological surgery and biochemistry at LLUSM, confer in the laboratory of the Neurosurgery Center for Research, Training and Education.
Matthew Scrag, a graduate student in the Loma Linda University School of Medicine (LLUSM), and Wolff Kirsch, MD, professor of neurological surgery and biochemistry at LLUSM, confer in the laboratory of the Neurosurgery Center for Research, Training and Education. Mr. Schrag and Dr. Kirsch are two of the four-member team of researchers from Loma Linda University and George Mason University who recently discovered a trail of biomarkers they hope will lead to the early detection of Alzheimer’s disease.



Neuroscience researchers at Loma Linda University School of Medicine (LLUSM) in California and George Mason University (GMU) in Virginia have found a trail of biomarkers they hope will lead to the early detection of Alzheimer’s disease.

Should that happen, the findings would rank among the greatest medical achievements of the new century.

“Rather than a single protein marker,” notes Claudius Mueller, PhD, “we found the whole heme degradation pathway to be a very promising source of serum biomarkers for the early detection of Alzheimer’s disease.” Heme‚Äîa key constituent of hemoglobin in red blood cells‚Äîis defined by an online dictionary from Princeton University as “a complex red organic pigment containing iron and other atoms to which oxygen binds.”

Dr. Mueller says the team used mass spectrometry to screen for low-abundance serum proteins and protein fragments, which he describes as “garbage shed into the blood,” in search of products connected to the existence of Alzheimer’s disease.

At the time the bulk of the research was conducted, Claudius Mueller was a graduate student affiliated with the Neurosurgery Center for Research, Training and Education (NCRTE) at LLUSM. He is currently a research assistant professor affiliated with the Center for Applied Proteomics & Molecular Medicine (CAPMM) at GMU. Proteomics is the large-scale study of protein structure and function.

Principal investigator Wolff M. Kirsch, MD—who is also a professor of neurological surgery and biochemistry at LLUSM, and founder of the NCRTE—describes the process in colorful terms.

“Inflammation of the brain causes a reaction,” Dr. Kirsch explains. “Blood cells break down and are digested by the body. These signal production of enzymes that break down the blood even more. Fragments of these enzymes are getting into the blood. It’s kind of like the Los Angeles Police Department in MacArthur Park. They bring out the billy clubs and in the process, there’s going to be some collateral damage.”

Lance Liotta, MD, professor of life sciences, and co-director of the CAPMM at GMU, notes that, "There is a great need to develop biomarkers for early stage Alzheimer's disease—the only time it may be treatable. This study provides some new candidates for that purpose."

LLUSM graduate student Matthew Schrag observes that, “A biomarker for the existence of Alzheimer’s would be the Holy Grail. The other Holy Grail would be a cure for the disease.”

The team of Dr. Mueller, Dr. Kirsh, Dr. Liotta and Mr. Schrag published its findings in the Journal of Alzheimer’s Disease, volume 19, pages 1081-91.

According to Dr. Mueller, the group is excited to be on the cusp of an important discovery. But have they found the Holy Grail of Alzheimer’s research?

The answer, he explains, is a resounding and qualified maybe.

“It is still too early to correctly evaluate the significance of our findings,” he says.
However, he stops far short of saying no.

“If, based on our discovery, we are able to diagnose Alzheimer’s disease before the onset of neurodegeneration,” Dr. Mueller adds, “then yes, this would turn out to be the Holy Grail.”

The idea for the study emerged from a 2005 dining room conversation between Dr. Kirsch, Dr. Mueller, and Rodney L. Levine, MD, principal investigator of the biochemistry laboratory at the National Heart, Lung, and Blood Institute.
Dr. Levine recommended that Dr. Kirsch contact Dr. Liotta.

To capitalize on the opportunity, Drs. Kirsch and Mueller flew to Virginia to meet Dr. Liotta, and the project was underway.

“Together with his colleagues, Dr. Liotta provided the needed proteomics expertise,” Dr. Mueller recalls. “He was instrumental in the experiment design process and also the analysis. We collected and analyzed a lot of data, but it wasn’t until December of 2008 that we were suddenly able to connect the dots.”

Currently, the team is hard at work trying to move the study to the next level. Like a proud papa, Dr. Kirsch is pleased with the group’s progress so far.

“The guys are doing a great job in the lab,” he beams. “They’re really doing beautiful work down there!”

By James Ponder