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VGF in Cerebrospinal Fluid Combined With Conventional Biomarkers Enhances Prediction of Conversion From MCI to AD

Llano, Daniel A. MD, PhD*,†; Devanarayan, Priya; Devanarayan, Viswanath PhD§,∥ for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Alzheimer Disease & Associated Disorders: October–December 2019 - Volume 33 - Issue 4 - p 307–314
doi: 10.1097/WAD.0000000000000328
Original Articles
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Background: Previous work has suggested that the brain and cerebrospinal fluid (CSF) levels of a neural protein involved in synaptic transmission, VGF (a noninitialism), may be altered in mild cognitive impairment (MCI) and Alzheimer Disease (AD). The objective of the current work is to examine the potential of CSF levels of a peptide derived from VGF to predict conversion from MCI to AD.

Materials and Methods: Using multivariate analytical approaches, the performance of the conventional biomarkers (CSF Aβ1-42 and phosphorylated tau +/− hippocampal volume) was compared with the same biomarkers combined with CSF VGF peptide levels in a large publicly available data set from human subjects.

Results: It was observed that VGF peptides are lowered in CSF of patients with AD compared with controls and that combinations of CSF Aβ1-42 and phosphorylated tau, hippocampal volume, and VGF peptide levels outperformed conventional biomarkers alone (hazard ratio=2.2 vs. 3.9), for predicting MCI to AD conversion.

Conclusions: CSF VGF enhances the ability of conventional biomarkers to predict MCI to AD conversion. Future work will be needed to determine the specificity of VGF for AD versus other neurodegenerative diseases.

*Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign

Carle Neuroscience Institute, Urbana

Department of Mathematics, Statistics and Computer Science, University of Illinois at Chicago, Chicago, IL

Souderton Area High School, Souderton

§Charles River Laboratories, Horsham, PA

Data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data, but did not participate in analysis or writing of this report. A complete listing of ADNI.investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech Inc.; Fujirebio; GE Healthcare; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co. Inc.; Meso Scale Diagnostics LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

V.D. is an employee of Charles River Laboratories, and as such owns equity in, receives salary and other compensation from Charles River Laboratories. V.D. received stocks from Charles River and AbbVie during the past 36 months. The remaining authors declare no conflicts of interest.

Reprints: Daniel A. Llano, MD, PhD, Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (e-mail: d-llano@illinois.edu).

Received April 3, 2019

Accepted May 17, 2019

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