Low Plasma Leptin in Cognitively Impaired ADNI Subjects: Gender Differences and Diagnostic and Therapeutic Potential

• Type of Material: Article
• Authors: Jane M. Johnston, Neurotez Inc.; William Hu, Emory University; David W. Fardo, University of Kentucky; Steven J. Greco, Neurotez Inc.; George Perry, University of Texas San Antonio; Thomas J. Montine, University of Washington; John Q. Trojanowski, University of Pennsylvania; Leslie M. Shaw, University of Pennsylvania; J. Wesson Ashford, Stanford University; Nikolaos Tezapsidis, Neurotez Inc.
• Language: English
• Date: 2014-02-01
• Publisher: Bentham Science Publications Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Bentham Science Publishers.
• Final Published Version (URL): http://dx.doi.org/10.2174/1567205010666131212114156
• Title of Journal or Parent Work: Current Alzheimer Research
• Volume: 11
• Issue: 2
• Start Page: 165
• End Page: 174
• Grant/Funding Information: 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 California, Los Angeles.; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904).; ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.;Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company.; Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada.; This research was also supported by NIH grants P30 AG010129 and K01 AG030514 and work at Neurotez was supported by the National Institute on Aging (SBIR-5R44AG029670).
• Keywords: Life Sciences & Biomedicine; apolipoprotein-E; Science & Technology; leptin replacement; Neurosciences; Association; Brain; Alzheimer's disease; Genotype; Obesity; Dementia; Alzheimer's disease neuroimaging initiative; Low CSF leptin; TAU phosphorylation; leptin; Neurosciences & Neurology; Clinical Neurology; Memory; Biomarkers; mild cognitive impairment
• Research Categories: Biology, Genetics; Health Sciences, Rehabilitation and Therapy; Health Sciences, Nutrition; Health Sciences, Health Care Management; Biology, Neuroscience

Abstract

Analysis of data derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) program showed plasma leptin levels in individuals with Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD) to be lower than those of subjects with normal cognition (NC). Approximately 70% of both men and women with MCI have plasma leptin levels lower than the median values of NC. Additionally, half of these subjects carry at least one apolipoprotein-E4 (APOE-ε4) allele. A subgroup of participants also had cerebrospinal fluid (CSF) leptin measured. Plasma leptin typically reflected the levels of leptin in CSF in all groups (Control/MCI/AD) in both genders. The data suggest that plasma leptin deficiency provides an indication of potential CNS leptin deficiency, further supporting the exploration of plasma leptin as a diagnostic marker for MCI or AD. The important question is whether leptin deficiency plays a role in the causation of AD and/or its progression. If this is the case, individuals with early AD or MCI with low plasma leptin may benefit from leptin replacement therapy. Thus, these data indicate that trials of leptin in low leptin MCI/early-stage AD patients should be conducted to test the hypothesis.