SILK-Abeta Study Detects Early Changes in Brain Amyloid Pathology
June 14, 2013ST. LOUIS - C2N Diagnostics today announced that its two co-founding scientists, Drs. Randall Bateman and David Holtzman, along with other colleagues from the Washington University School of Medicine have independently published a pivotal clinical study that appeared in the June 12th online edition of Science Translational Medicine. The publication(1), entitled “Increased in Vivo Amyloid-beta 42 Production, Exchange, and Loss in Presenilin Mutation Carriers”, presents the first study of its kind in humans.
Individuals who carry genetic mutations predisposing to early Alzheimer’s Disease (AD) as well as their siblings without the mutation (serving as controls) each underwent stable isotope labeled kinetic (SILK) testing to measure amyloid beta (Abeta ) metabolism within the brain. These SILK-derived measures were then compared with mutation status as well as the amount of amyloid deposition in the brain using PET amyloid imaging. Results were striking.
Production rates of Abeta 42 – the specific form of Abeta believed to associate closest with amyloid plaque accumulation – were about 20% higher in mutation carriers, regardless of how much amyloid they had in the brain. The rate at which Abeta 42 disappeared from the cerebrospinal fluid was also considerably faster in mutation carriers. This abnormal kinetic profile was present in most mutation carriers who had no visible plaques detectable by PET amyloid imaging, suggesting that the SILK method was more sensitive at picking up early disease changes than amyloid imaging alone. As amyloid burden in the brain increased, Abeta 42 disappearance became significantly faster and changed in a highly quantitative and predictable manner.
As a result of the SILK data collected in the study, the authors were able to develop a unique mathematical model to explain steady-state Abeta isoform kinetics. The model describes fundamental processes that affect Abeta metabolism, including normal and abnormal physiological conditions. The model also provides new insights into pre-symptomatic disease progression among individuals genetically predisposed to AD. Results from the study suggest that SILK-derived measurements hold promise for not only detecting disease early, but also guiding early AD treatment and prevention strategies.
(1) R. Potter, B.W. Patterson, D.L. Elbert, V. Ovod, T. Kasten, W. Sigurdson, K. Mawuenyega, T. Blazey, A. Goate, R. Chott, K.E. Yarasheski, D.M. Holtzman, J.C. Morris, T.L.S. Benzinger, R.J. Bateman. Increased in vivo amyloid-Abeta 42 production, exchange, and loss in presenilin mutation carriers. Sci Transl Med 5, 189ra77 (2013). Link to text: http://stm.sciencemag.org/content/5/189/189ra77
About C2N Diagnostics
C2N Diagnostics, LLC (www.c2ndiagnostics.com) formed in late 2007 by scientific co-founders Drs. David Holtzman and Randall Bateman of Washington University School of Medicine in St. Louis, the Washington University Office of Technology Management, and LifeTech Research, a Maryland-based technology research and commercialization firm (www.lifetechresearch.com). C2N is developing a suite of novel biomarker assays and tools to assist in pre-clinical drug discovery, clinical drug development, and the early detection and assessment of progression of debilitating neurodegenerative disorders. The company’s products include the SILK-Aβ®, SISAQ-Aβ™, and SISAQ-Tau™ Assays, which rely upon stable isotope labeling and tandem mass spectrometry for the measurement of the kinetics, or in vivo metabolism, and absolute quantitation of brain derived proteins. Beyond AD, products are in development to target Parkinson’s disease, Huntington’s disease, brain injury, schizophrenia, and amyotrophic lateral sclerosis (ALS), among others. For additional information, please contact info@c2ndiagnostics.com or call 1-877-C2N-DIAG (1-877-226-3424).