Bret S. Stetka, MD


April 01, 2013

In This Article

Biomarkers in Alzheimer' Disease: Introduction

On the morning of Monday, March 18, at the 65th Annual Meeting of the American Academy of Neurology, conference-goers packed an Integrative Neuroscience Session for an update on the state of biomarker research in Alzheimer disease (AD). "Alzheimer's Biomarkers in Clinical Practice"[1] brought together leading researchers in the field to discuss how biomarker advances have already affected and will further affect the understanding, diagnosis, and, ultimately, the care of patients with AD.

Program Director Gil D. Rabinovici, MD, Assistant Professor of Neurology at the Memory and Aging Center, University of California, San Francisco, started off the session with an introduction and brief history of biomarker research in AD. Rabinovici cited the first AD diagnostic guidelines, released in 1984 by the National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (now the Alzheimer's Association) which, not surprisingly, did not include any biomarker criteria. Contrast this to 2013, in which multiple AD biomarkers are receiving research attention, including structural and metabolic brain alterations as well as amyloid and tau protein levels in both the brain and cerebrospinal fluid (CSF).

Giovanni Frisoni, MD, from San Giovanni di Dio Fatebenefratelli in Brescia, Italy, delivered the first talk, addressing the clinical role of brain atrophy measures in AD diagnosis. Dr. Frisoni pointed out that hippocampal volume reduction can distinguish AD in an aggregate patient sample but not at the individual level -- therefore, not in a clinically meaningful way. However, he did cite a somewhat striking study by Prestia and colleagues[2] assessing for hippocampal atrophy, decreased CSF amyloid, and decreased brain glucose metabolism in 73 patients with mild cognitive impairment. Among those with no positive biomarkers, only 4% went on to develop AD, while in those positive for all 3, 100% ultimately progressed to AD. Study limitations included a relatively short follow-up time (12-84 months; presumably additional patients would have converted with continued follow-up) and a small sample size.

A key takeaway from Dr. Frisoni's talk was the need for clinical laboratories and for the AD research community to standardize biomarker measurement protocols in both the United States and abroad, citing marked differences in technique and subsequent variable results. "How you measure biomarkers is more important than what biomarkers you use," he commented.