Blood Test Identifies Seniors At-Risk for Cognitive Impairment or Alzheimer's Years in Advance of Onset

A team of researchers has discovered biomarkers and validated the first blood test that accurately predicted whether an asymptomatic person will develop amnestic mild cognitive impairment or Alzheimer’s disease within 3 years before onset of clinical symptoms, heralding the potential for developing treatment strategies to prevent, reverse, or slow disease progression.

In a collaborative study between several institutions, mainly Georgetown University Medical Center (GUMC; Washington DC, USA) and University of Rochester School of Medicine (URSM; Rochester, NY, USA), a blood-based biomarker panel has been discovered that may identify preclinical Alzheimer's disease. In the report, published in the journal Nature Medicine, March 9, 2014, online ahead of print, Mapstone et al. describe their lipidomic approach examining cognitively normal senior adults. They discovered and validated a set of lipids from peripheral blood plasma that predicted with over 90% accuracy the phenoconversion within 2-3 years from cognitively normal to either amnestic mild cognitive impairment (aMCI) or on to Alzheimer's disease (AD).

The study has yielded the first blood test that accurately identified individuals at risk for developing AD. The discovery could be a key to unlocking a new generation of treatments that seek to head off the disease before neurological damage becomes irreversible. “Our novel blood test offers the potential to identify people at risk for progressive cognitive decline and can change how patients and their families, and treating physicians plan for and manage the disorder,” said corresponding author Howard J. Federoff, MD, PhD, professor of neurology at the GUMC. Some of the same experimental treatments that have thus far failed may prove to be successful if they are given to high-risk patients much sooner.

Biomarkers of preclinical disease with high sensitivity and specificity are critical. Current biomarkers and methods used in attempt to detect early disease are very limited. For widespread use and large-scale screening, blood-based biomarker screening would be more attractive and may also be more effective.

The study included 525 asymptomatic participants aged 70 years and older. In the 5-year study, 74 participants met the criteria either for mild AD or for aMCI. Of these, 46 were diagnosed already upon enrollment and 28 developed aMCI or mild AD during the study (those of the latter group were called converters). In the third year, 53 participants who developed aMCI/AD (including 18 converters) and 53 cognitively normal matched controls were selected for the lipid biomarker discovery phase of the study.

Using mass spectrometry, 10 lipids were identified that, if present in lower than normal blood plasma levels, predicted with more than 90% accuracy whether an individual would go on to develop AD or aMCI. All 10 are phospholipids. The 10-lipid panel was validated using the remaining 21 aMCI/AD participants (including 10 converters), and 20 controls. The lipid panel again distinguished with 90% accuracy.

The study also examined the APOE4 gene, an accepted risk factor for AD, but it was not a significant predictive factor in this study.

“The ability to identify individuals who are at risk of developing Alzheimer’s before the clinical manifestation of cognitive impairment has long been a Holy Grail of the neuromedicine community,” said lead author Mark Mapstone, PhD, neuropsychologist at the URSM; “Biomarkers that can allow us to intervene early in the course of the disease could be a game-changer.” He added, “Having a tool that is able to identify, with a high degree of accuracy and at a low cost, which individuals will convert to Alzheimer’s could transform how we care for this devastating disease.”

Related Links:
Georgetown University Medical Center
University of Rochester School of Medicine