Abstract
Back to table of contents Previous article Next article Clinical & Research NewsFull AccessBeta-Amyloid Findings Could Be Alzheimer's MarkerAaron LevinAaron LevinSearch for more papers by this authorPublished Online:3 Feb 2006https://doi.org/10.1176/pn.41.3.0020The Holy Grail for researchers studying Alzheimer's disease is an imaging system or biomarker to help diagnose the illness or at least document its progress.A new study from researchers at Washington University in St. Louis takes a step in that direction by combining PET scan imaging and cerebrospinal fluid (CSF) analysis. The process compared the extent of beta-amyloid plaques in the brain with levels of related protein fragments in CSF or blood plasma.Using PET technology, researchers led by Anne Fagan, Ph.D., a research associate professor of neurology at the Washington University School of Medicine, scanned the brains of 24 people aged 48 to 83 to find concentrations of plaques containing beta-amyloid. They used an amyloid-binding agent, Pittsburgh Compound B (PIB), provided by investigators at the University of Pittsburgh. Some participants were cognitively normal while others had very mild, mild, or moderate dementia.Fagan and her colleagues from the Washington University Alzheimer's Disease Research Center also tested CSF and blood plasma for several proteins using enzyme-linked immunosorbent assays.They found no relation between PIB binding and the proteins amyloid-40, tau, phosphor-tau181 in CSF, and amyloid-40 and amyloid-42 in plasma. However, they did observe an inverse relationship between amyloid-42 in CSF and PIB binding at beta-amyloid plaques in the brain.“Subjects fell into two nonoverlapping groups: those with positive PIB binding had the lowest CSF amyloid-42 level, and those with negative PIB binding had the highest level,” wrote the researchers in an online publication of their paper in the Annals of Neurology.Seven subjects showed positive PIB binding and low CSF amyloid-42 levels. Three of those subjects were diagnosed with mild or moderate Alzheimer's-type dementia, and another with very mild symptoms.However, three participants were cognitively normal but had high PIB binding and low CSF levels of amyloid-42, hinting that they were in such a preclinical state. If these subjects eventually develop dementia, this combined technique may indeed prove useful for identifying cases before they reach clinical status. However, if patients such as these never decline cognitively, it may show that plaque number does not always predict the disease.Prior animal studies have suggested that amyloid plaques in the brain may bind beta-amyloid, reducing the movement of soluble beta-amyloid between the brain and the CSF, possibly accounting for the inverse relationship, said the authors. Heavy deposits of beta-amyloid plaques at autopsy are diagnostic for Alzheimer's disease.“These observations suggest that brain amyloid deposition results in low CSF amyloid-42 and that amyloid imaging and CSF amyloid-42 levels may potentially serve as antecedent biomarkers of preclinical Alzheimer's disease,” Fagan said. “[They] support the hypothesis that amyloid deposition in the brain acts as a `sink,' resulting in a new equilibrium between soluble and deposited amyloid-42 in the central nervous system.”“These measures hold potential for identifying individuals with Alzheimer's disease pathology before cognitive symptoms [appear], improving the accuracy of clinical diagnosis, and facilitating the testing of future therapies,” said Fagan in a prepared statement. “But it is important to recognize that this is still a research study, and the findings must be carefully validated before this approach can be considered for clinical use.”“We presently don't have fully validated imaging or biomarker measures that can help us monitor the development or progression of Alzheimer's in living people,” commented Neil Buckholtz, Ph.D., chief of the Dementias of Aging Branch at the National Institute on Aging. “This study represents one step in the progress being made toward identifying clinically useful biological measures for AD.”The study was supported by the National Institute on Aging and the Washington University General Clinical Research Center, which is funded by the National Institutes of Health.An abstract of “Inverse Relation Between in Vivo Amyloid Imaging Load and Cerebrospinal Fluid A42 in Humans” is posted at<www3.interscience.wiley.com/cgi-bin/abstract/112219062/ABSTRACT>.▪ ISSUES NewArchived
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