CLN Article

A New Look at Alzheimer’s Disease

Leading Researchers Detail Scientific, Analytic Advances

Genna Rollins

Though clinicians right now have little to offer Alzheimer's disease patients, considerable progress has been made in understanding this devastating chronic disease of aging, and in developing a diagnostic testing infrastructure that will be important when Alzheimer's-related biomarkers come into common use clinically. Those were key points from the symposium, "The Use of Biomarkers in Detection of Alzheimer's Disease," presented at the 2013 AACC Annual Meeting by two highly respected researchers in the field, Joy Snider, MD, PhD, and Leslie Shaw, PhD.

"The bottom line for laboratorians is that more patients and diagnostic tests are on the way, so you need to be aware of the latest science in this field. I hope that laboratories can serve as the front line in helping clinicians understand and interpret these tests, because we have a lot of patients coming," said Snider, an associate professor of neurology at the Washington University School of Medicine in St. Louis.

She reminded the audience that physicians can only make a presumptive diagnosis of Alzheimer's disease based on clinical history.

Snider explained that while commercial tests for Alzheimer's biomarkers are available, proper use and interpretation of them remains challenging. "When they're elevated they could tell you Alzheimer's is a likely cause if the person has cognitive changes, but if the patient is normal, they don't tell you for sure the person will develop symptoms," she said. The field lacks enough information about these markers to give clinically meaningful interpretation in cognitively normal people, so testing in this population is not recommended, Snider added.

Charting the Natural History

Both she and Shaw reviewed what is known about the natural history of Alzheimer's. Long before patients experience any symptoms, the protein tau hyperphosphorylates, leading to neuronal cell death and characteristic tangles in the brain. Later on, amyloid beta protein builds in the brain, forming plaques.

"It's thought that these two primary processes are relatively independent of one another, at least at their onset. However, at some point in time they intersect," Shaw explained. "Then one can ask, does one type of pathology exacerbate the other? That's a current hypothesis that needs to be tested." He is a professor of pathology and laboratory medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia, and was honored at the 2013 AACC Annual Meeting and Clinical Lab Expo with the outstanding lifetime achievement award in clinical chemistry and laboratory medicine.

Shaw went on to outline numerous technical and analytical advancements from the landmark Alzheimer's Disease Neuroimaging Initiative (ADNI) clinical trial and several follow-on studies. ADNI researchers standardized a process for performing lumbar puncture (LP) and processing cerebrospinal fluid specimens (CSF), so that LP participation rates—initially planned to be 20%—are as high as 90% in certain ADNI studies. Similarly, ADNI investigators took pains to standardize pre-analytical CSF preparation as well as CSF analysis. The research team has conducted several analytical studies, including comparing inter-lab performance and immunoassay versus mass spectrometry methods in measuring Alzheimer's-related biomarkers. Proficiency testing for these biomarkers, sponsored by the Alzheimer's Association, also has been developed. In addition, Shaw's lab and others have been involved in research to establish cutpoints for amyloid beta and tau indicative of progression to Alzheimer's disease, parameters of importance to pharmaceutical manufacturers running clinical trials of potential treatments for the disease.

"Looking at the future of this area, the infrastructure is being built step-by-step to the point where providing high-quality CSF specimens and processing will be very much an expectation of those following these patients," said Shaw.