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Insulin-like growth factor binding protein-2 interactions with Alzheimer’s disease biomarkers

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Abstract

Plasma levels of insulin-like growth factor binding protein-2 (IGFBP-2) have been associated with Alzheimer’s disease (AD) and brain atrophy. Some evidence suggests a potential synergistic effect of IGFBP-2 and AD neuropathology on neurodegeneration, while other evidence suggests the effect of IGFBP-2 on neurodegeneration is independent of AD neuropathology. Therefore, the current study investigated the interaction between plasma IGFBP-2 and cerebrospinal fluid (CSF) biomarkers of AD neuropathology on hippocampal volume and cognitive function. AD Neuroimaging Initiative data were accessed (n = 354, 75 ± 7 years, 38 % female), including plasma IGFBP-2, CSF total tau, CSF Aβ-42, MRI-quantified hippocampal volume, and neuropsychological performances. Mixed effects regression models evaluated the interaction between IGFBP-2 and AD biomarkers on hippocampal volume and neuropsychological performance, adjusting for age, sex, education, APOE ε4 status, and cognitive diagnosis. A baseline interaction between IGFBP-2 and CSF Aβ-42 was observed in relation to left (t(305) = −6.37, p = 0.002) and right hippocampal volume (t(305) = −7.74, p = 0.001). In both cases, higher IGFBP-2 levels were associated with smaller hippocampal volumes but only among amyloid negative individuals. The observed interaction suggests IGFBP-2 drives neurodegeneration through a separate pathway independent of AD neuropathology.

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Acknowledgments

F32-AG046093 (EML), R01-AG034962 (ALJ), R01-HL111516 (ALJ), K24-AG046373 (ALJ), K12-HG043483 (TJH), Vanderbilt Memory & Alzheimer’s Center; 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 National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, and generous contributions from: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; 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.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. 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 Northern California Institute for Research and Education, and study is coordinated by Alzheimer’s Disease Cooperative Study at University of California, San Diego. ADNI data are disseminated by Laboratory for Neuro Imaging at University of Southern California.

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  1. Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, 1207 17th Avenue South, Suite 204, Nashville, TN, 37212, USA

    Elizabeth M. Lane, Timothy J. Hohman & Angela L. Jefferson

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  1. Elizabeth M. Lane
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  2. Timothy J. Hohman
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Correspondence to Angela L. Jefferson.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Additional information

Data used in 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 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

Highlights

• IGFBP-2 and AD biomarkers interact on hippocampal volume

• Higher IGFBP-2 relate to smaller hippocampi among amyloid negative individuals

• The effects of IGFBP-2 may drive neurodegeneration through independent, non-AD pathways

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Lane, E.M., Hohman, T.J., Jefferson, A.L. et al. Insulin-like growth factor binding protein-2 interactions with Alzheimer’s disease biomarkers. Brain Imaging and Behavior 11, 1779–1786 (2017). https://doi.org/10.1007/s11682-016-9636-0

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