36 research outputs found
Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease
Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions
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The Date of Three Turkey House
This item is part of the Tree-Ring Research (formerly Tree-Ring Bulletin) archive. It was digitized from a physical copy provided by the Laboratory of Tree-Ring research at The University of Arizona. For more information about this peer-reviewed scholarly journal, please email the Editor of Tree-Ring Research at [email protected]
Prehistoric Indians of the Southwest. H. M. Wormington. Popular Series, Colorado Museum of Natural History, No. 7. Denver, 1947. 191 pp., 58 figures.
Anasazi Painted Pottery in Field Museum. Paul S. Martin and Elisabeth Willis (Anthropology Memoirs, Field Museum of Natural History, Vol. 5, Chicago, December 31, 1940.)
Starkweather Ruin: A Mogollon-Pueblo site in the Upper Gila area of New Mexico, and affiliative aspects of the Mogollon Culture. Paul H. Nesbitt. (Logan Museum Publications in Anthropology. Bulletin No. 6, The Logan Museum, Beloit College, Beloit, Wisconsin. 1938. Pp. 143. 6 text figures, 50 plates.)
Prehistoric Pottery of the Eastern United States. Edited by James B. Griffin. University of Michigan, Museum of Anthropology, Ann Arbor, 1950-1954. Issued in parts. Illus. $2.50 (to date, by subscription).
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Book Reviews
This item is part of the Tree-Ring Research (formerly Tree-Ring Bulletin) archive. It was digitized from a physical copy provided by the Laboratory of Tree-Ring research at The University of Arizona. For more information about this peer-reviewed scholarly journal, please email the Editor of Tree-Ring Research at [email protected]