Another biomarker emerging for Alzheimer's
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The search for Alzheimer's disease biomarkers goes on, with a number of biomarkers beginning to emerge. The latest research focuses on biomarkers that signal damage to neurons, which might allow doctors to spot decline at an early stage. In the research published in Neurology, a team from Washington University School of Medicine in St. Louis measured biomarkers in the cerebrospinal fluid (CSF) from lumbar punctures in people with very mild or mild Alzheimer's disease over an average of 2.6 years. They measured the biomarkers visinin-like protein-1 (VILIP-1), tau, p-tau181 and Aß42 (amyloid beta), as well as tracking changes in mental activity and memory with annual assessments.
VILIP-1 measures damage to brain cells, and tau and Aß42 reflect the plaques starting to form in the brain. Alzheimer's disease in people with higher levels of these biomarkers, particularly VILIP-1, progressed more quickly.
"VILIP-1 appears to be a strong indicator of ongoing injury to brain cells as a result of Alzheimer's disease. Memory and other mental abilities declined faster in patients with the highest levels of VILIP-1," says lead author Dr. Rawan Tarawneh, now at the University of Jordan. "In patients with early symptoms of Alzheimer's disease, VILIP-1 seems to be at least as good as--and potentially even better than--the other prognostic indicators we used in the study. That could be very useful in predicting the course of the disease and in evaluating new treatments in clinical trials."
This research is early but shows promise for predicting disease progression and prognosis, and tracking outcomes in clinical trials, and further development is under way at Washington University. However, it is still a CSF-based biomarker, and until simple blood-based biomarker tests are available, broader screening for Alzheimer's disease to allow early diagnosis and treatment isn't really going to be feasible.
--- The Neurology article ---
CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease
Neurology March 6, 2012 78:709-719; published ahead of print February 22, 2012,
R. Tarawneh, MD, J.-M. Lee, MD, PhD, J.H. Ladenson, PhD, J.C. Morris, MD and D.M. Holtzman, MD
Author Affiliations
From the Department of Neurology (R.T., J.-M.L., J.C.M., D.M.H.), Hope Center for Neurological Disorders (R.T., J.-M.L., D.M.H.), Charles F. and Joanne Knight Alzheimer’s Disease Research Center (R.T., J.C.M., D.M.H.), Department of Pathology and Immunology (J.H.L.), and Department of Developmental Biology (D.M.H.), Washington University School of Medicine, St. Louis, MO. Correspondence & reprint requests to Dr. Holtzman: holtzman@neuro.wustl.edu
Abstract
Objective: Measures of neuronal damage/dysfunction are likely good surrogates for disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may offer utility in predicting disease progression and guiding prognostic and outcome assessments in therapeutic trials. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. We here investigate the utility of VILIP-1 and VILIP-1/Aß42 in predicting rates of cognitive decline in early AD.
Methods: Individuals with a clinical diagnosis of very mild or mild AD (n = 60) and baseline CSF measures of VILIP-1, tau, p-tau181, and Aß42 were followed longitudinally for an average of 2.6 years. Annual assessments included the Clinical Dementia Rating (CDR), CDR–sum of boxes (CDR-SB), and global composite scores. Mixed linear models assessed the ability of CSF biomarker measures to predict rates of cognitive decline over time.
Results: Baseline CSF VILIP-1 and VILIP-1/Aß42 levels predicted rates of future decline in CDR-SB and global composite scores over the follow-up period. Individuals with CSF VILIP-1 =560 pg/mL (corresponding to the upper tercile) progressed much more rapidly in CDR-SB (1.61 boxes/year; p = 0.0077) and global scores (-0.53 points/year; p = 0.0002) than individuals with lower values (0.85 boxes/year and -0.15 points/year, respectively) over the follow-up period. CSF tau, p-tau181, tau/Aß42, and p-tau181/Aß42 also predicted more rapid cognitive decline in CDR-SB and global scores over time.
Conclusion: These findings suggest that CSF VILIP-1 and VILIP-1/Aß42 predict rates of global cognitive decline similarly to tau and tau/Aß42, and may be useful CSF surrogates for neurodegeneration in early AD.
Received July 12, 2011. Accepted October 26, 2011. Copyright © 2012 by AAN Enterprises, Inc. |
