PARIS—Using blood biomarkers, researchers were able to identify persons at high risk for Alzheimer’s disease with a specificity of 85%, providing an initial step toward the development of a cost-effective and accessible blood test. In a separate study, a team of investigators accurately predicted conversion from mild cognitive impairment (MCI) to Alzheimer’s dementia up to 10 years before the onset of dementia based on a CSF test for three Alzheimer’s-related proteins.
The two studies, which were presented by CSIRO scientist Samantha Burnham, PhD, from the Australian Imaging Biomarkers and Lifestyle (AIBL) study of aging in Perth, Australia, and Henrik Zetterberg, MD, PhD, from the University of Gothenburg, Sweden, respectively, at the 2011 Alzheimer’s Association International Conference, suggest that biomarkers in the blood and CSF may be the key to developing reliable prognostic tests for early diagnosis of Alzheimer’s disease. These tests could also be useful in quantifying the severity of disease and in judging the effectiveness of therapeutic tests, assessments, or lifestyle interventions.
A Blood Test for Alzheimer’s Disease?
“Often individuals are classified as having high or low amyloid-loading based on Pittsburgh Compound-B [PiB]-PET imaging, with those having high amyloid-loading suspected to be at risk of developing Alzheimer’s disease,” Dr. Burnham told Neurology Reviews. “If this is the case, then indicators of the amount of the plaque in the brain could represent early indicators of the disease.”
To investigate the feasibility of using blood biomarkers to diagnose Alzheimer’s disease, AIBL researchers, led by Professors David Ames, Colin Masters, Ralph Martins, Chris Rowe, and Ashley Bush, assessed the blood chemistry, lifestyle, and cognitive function of 1,112 persons (768 cognitively normal individuals, 133 with mild cognitive impairment, and 211 with Alzheimer’s disease) at baseline and 18 months. Neuroimaging and genetic testing were performed on a subset of 288 participants.
“We took 272 of the subjects whom we had imaged and tried to find some blood measurements that told us how much plaque somebody has in his or her brain based on these blood measurements,” Dr. Burnham said.
The researchers created a model of nine blood-based biomarkers, including amyloid-beta 42, apolipoprotein E (APOE), and cortisol, to estimate the amount of deposited amyloid in the brain.
Dr. Burnham, as part of the AIBL Biomarkers team, compared index scores based on the identified biomarkers with actual clinical diagnoses and imaging results and found significant correlations.
According to the model, 34% of the cognitively normal group, 87% of the group with mild cognitive impairment, and 100% of the group with Alzheimer’s disease should have had high loads of amyloid plaques. “About one-third of healthy controls, two-thirds of those who were mildly cognitively impaired, and nearly all of the Alzheimer’s disease patients [had] high loading of plaque in the brain,” reported Dr. Burnham. “In terms of sensitivity and specificity, we’re at the 83% to 85% mark.” Similar percentages were observed when the investigators applied the biomarker panel to the 800 participants who had not undergone imaging.
When the researchers looked at data from those participants who had transitioned to Alzheimer’s disease during the study period, they found that 100% of those who were healthy controls and 97% of those with MCI at baseline were predicted to have high amyloid burden.
Using Blood-Based Biomarkers to Determine Disease Severity
“The panel of biomarkers works together to provide the correlation with amyloid-loading of the neocortex,” Dr. Burnham explained. “Not all of the markers are effective or significant at predicting amyloid-loading on their own, but work in conjunction with each other to provide the correlation.” She did note, though, that when APOE and amyloid-beta 42 were removed from the blood biomarker panel, the efficacy of the test was reduced.
“The specific research presented shows a correlation between a panel of blood-based markers and amyloid-loading in the neocortex as imaged by PiB-PET,” said Dr. Burnham. “If the amount of amyloid-loading in the neocortex is an indicator of how far along a person is in the disease process, then this blood test may have use in gauging disease severity.
“If the findings can be validated and formatted to a suitable medium for widespread use,” Dr. Burnham continued, “this work may eventually lead to an effective and economical screen for early detection of individuals at risk of developing Alzheimer’s disease, allowing optimum treatment and intervention strategies to be employed.”
Measuring Amyloid and Tau Proteins in CSF
According to Dr. Zetterberg, previous studies have shown that three proteins—total-tau, phospho-tau, and amyloid-beta 42—that are found in the CSF can accurately identify MCI due to Alzheimer’s disease up to 10 years before conversion to Alzheimer’s dementia.