title: Metabolic and hormonal signatures in pre-manifest and manifest Huntington's disease patients.
abstract: Huntington's disease (HD) is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG) expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be "pre-manifest." Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids, and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon, and amylin were also observed. Total cholesterol, HDL-C, and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.
authors.affiliation: Metabolism Unit, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine Baltimore, MD, USA ; Departments of Neuroscience and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine Baltimore, MD, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.affiliation: Metabolism Unit, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Cai
authors.affiliation: Metabolism Unit, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Cong
authors.affiliation: Metabolism Unit, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Daimon
authors.affiliation: Diabetes Section, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Olga D
authors.initials: OD
authors.lastname: Carlson
authors.affiliation: Diabetes Section, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.affiliation: Receptor Pharmacology Unit, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Sana
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: VIB Department of Molecular Genetics, University of Antwerp Antwerpen, Belgium.
authors.forename: Stuart
authors.initials: S
authors.lastname: Maudsley
authors.affiliation: Metabolism Unit, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Bronwen
authors.initials: B
authors.lastname: Martin
keywords: Huntington's disease; lipids; metabolic hormones; peripheral energy metabolism; pre-manifest