Bret S. Stetka, MD


April 01, 2013

In This Article

What's in a Lumbar Puncture?

Next on the schedule was William Jagust, MD, from the Helen Wills Neuroscience Institute at University of California, Berkeley, who spoke about the role of brain glucose metabolism measures as a biomarker for AD, specifically as a way to assess a patient's cognition. This "behavioral phenotype," as Dr. Jagust refers to it, cannot be gleaned from amyloid beta imaging; however, this information can be obtained using PET scans with a radiolabeled glucose analog (FDG-PET). FDG-PET technology can image brain metabolism in real time, providing a proxy measure of regional brain activity. Such studies have shown that glucose metabolism is reduced in most patients with AD.

"[But] what does FDG-PET add?" Dr. Jagust asked the audience. "Eighty-four percent of patients with a positive FDG-PET scan have corresponding AD pathology," he continued, "versus only 70% of those without evidence of cortical hypometabolism." These findings suggest that FDG-PET scans can potentially improve diagnostic accuracy. Also, whereas amyloid PET imaging reveals a patient's pathology, FDG-PET provides a better marker of clinical status and disease progression.

Program co-director Douglas R. Galasko, MD, of the University of California, San Diego, then reported on the diagnostic role of CSF biomarkers in AD. Patients with AD typically have a selective reduction in CSF amyloid beta 42, the brain effectively acting as a "sink" for the molecule. Conversely, tau and phosphorylated-tau (p-tau) are excessively released from the brain and into the CSF in patients with AD, with an increase in total tau representing neuronal damage and increased p-tau reflecting neurofibrillary tangle formation. Dr. Galasko then reviewed lumbar puncture practicalities, from the appropriate assay hardware -- polypropylene tubes minimize amyloid beta absorbance and retention -- to data supporting early-morning lumbar puncture because of diurnal variation in CSF biomarkers levels. He expressed skepticism about this finding but recommends morning procedures for the sake of standardization.

Dr. Galasko also seconded Dr. Frisoni's call to standardize biomarker assays, noting the great deal of variability in CSF biomarker measurements around the world: "We need to make sure that a measurement from Sweden means the same thing as a measurement from New York." He closed his talk by pointing out that almost all patients with AD have low CSF amyloid beta and high CSF tau levels, information that can provide diagnostic reassurance. CSF biomarkers can potentially provide a more definitive diagnosis and facilitate earlier treatment in those with mild symptoms who are at greater risk for converting to AD. But keep in mind that a small percentage of patients with non-AD dementia diagnoses will have positive CSF AD biomarkers.