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[P1–273]: QUANTIFICATION OF HEPCIDIN‐25 IN HUMAN CEREBROSPINAL FLUID: TECHNICAL FEASIBILITY AND BIOLOGICAL RELEVANCE IN NEURODEGENERATIVE DISEASES
Author(s) -
Delaby Constance,
Bros Pauline,
Vialaret Jérôme,
Catteau Cyndi,
Moulinier Amandine,
Picas Alexia,
Delatour Vincent,
Gabelle Audrey,
Dauvilliers Yves,
Geny Christian,
Hirtz Christophe,
Lehmann Sylvain
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.289
Subject(s) - hepcidin , cerebrospinal fluid , medicine , clinical significance , hemochromatosis , gastroenterology , anemia
Background: Frontotemporal dementia (FTD) is a progressive, neurodegenerative disorder with clinical and pathological heterogeneity. The main clinical FTD phenotypes are behavioural variant FTD (bvFTD), semantic dementia (SD) and progressive nonfluent aphasia (PNFA). One of the key clinical characteristics of bvFTD is disturbance in eating behaviour, which can be helpful in diagnosing bvFTD and differentiating it from Alzheimer’s disease (AD). The aim of this study was to develop a hypothalamic peptide panel, focusing on measures known to be involved in appetite regulation, to gain a better understanding of the pathophysiology of FTD, and potentially leading to better fluid biomarkers. Methods: A peptide multiplex panel of 13 hypothalamic and 9 peripheral appetite regulating peptides was developed on a liquid chromatography coupled tandemmass spectrometry platform. Concentrations were measured in the CSF of the three clinical FTD phenotypes (bvFTD n1⁄49, SD n1⁄49, PNFA n1⁄44) as well as AD (n1⁄44) and healthy controls (n1⁄46) and compared using non-parametric statistical tests. Results: In five of the hypothalamic peptides there was a significant difference (expressed as pmol/300 ml) between controls and at least one of the FTD groups (p<0.05): neuropeptideW levels were significantly higher in all three groups: bvFTD (0.029), SD (0.034) and PNFA (0.039), controls (0.012); cerebellin was decreased in bvFTD (0.586) and SD (0.591) [controls 0.945], and cocaine-amphetamine regulated transcript was decreased in PNFA (0.359) and SD (0.359) [controls 0.575]; corticotropinreleasing hormone was decreased in bvFTD (0.007) [controls 0.011] and galanin was increased in PNFA (0.107) [controls 0.059]. There was also a trend of decreased levels of pro-orexin in bvFTD. There were also significant differences in two of the peripheral peptides in PNFA (insulin-like growth factor 1 and pancreatic polypeptide). Conclusions: This pilot study shows changes in concentration of a substantial proportion of the hypothalamic peptides within the CSF in the FTD groups compared to controls. Further exploration on a larger clinically defined cohort will enable understanding of the differences in hypothalamic peptides in FTD and investigate whether such a panel could be used as a biomarker in FTD disease diagnosis, prognosis or stratification.