title: HNK-1 Carrier Glycoproteins Are Decreased in the Alzheimer's Disease Brain.
abstract: The human natural killer-1 (HNK-1), 3-sulfonated glucuronic acid, is a glycoepitope marker of cell adhesion that participates in cell-cell and cell-extracellular matrix interactions and in neurite growth. Very little is known about the regulation of the HNK-1 glycan in neurodegenerative disease, particularly in Alzheimer's disease (AD). In this study, we investigate changes in the levels of HNK-1 carrier glycoproteins in AD. We demonstrate an overall decrease in HNK-1 immunoreactivity in glycoproteins extracted from the frontal cortex of AD subjects, compared with levels from non-demented controls (NDC). Immunoblotting of ventricular post-mortem and lumbar ante-mortem cerebrospinal fluid with HNK-1 antibodies indicate similar levels of carrier glycoproteins in AD and NDC samples. Decrease in HNK-1 carrier glycoproteins were not paralleled by changes in messenger RNA (mRNA) levels of the enzymes involved in the synthesis of the glycoepitope, β-1,4-galactosyltransferase (β4GalT), glucuronyltransferases GlcAT-P and GlcAT-S, or sulfotransferase HNK-1ST. Over-expression of amyloid precursor protein in Tg2576 transgenic mice and in vitro treatment of SH-SY5Y neuroblastoma cells with the amyloidogenic Aβ42 peptide resulted in a decrease in HNK-1 immunoreactivity levels in brain and cellular extracts, whereas the levels of soluble HNK-1 glycoproteins detected in culture media were not affected by Aβ treatment. HNK-1 levels remain unaffected in the brain extracts of Tg-VLW mice, a model of mutant hyperphosphorylated tau, and in SH-SY5Y cells over-expressing hyperphosphorylated wild-type tau. These results provide evidence that cellular levels of HNK-1 carrier glycoforms are decreased in the brain of AD subjects, probably influenced by the β-amyloid protein.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Spain. ms.garcia@umh.es.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain. ms.garcia@umh.es.|Unidad de Investigación, Hospital General Universitario de Elche, FISABIO, Elche, Spain. ms.garcia@umh.es.
authors.forename: María-Salud
authors.initials: MS
authors.lastname: García-Ayllón
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Botella-López
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cuchillo-Ibañez
authors.affiliation: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.|Banco de Tejidos de la Fundación CIEN, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rábano
authors.affiliation: Karolinska Institute-Alzheimer Disease Research center, Stockholm, Sweden.
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.|Centro de Biología Molecular "Severo Ochoa", Universidad, Autónoma de Madrid, Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ávila
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Spain. j.saez@umh.es.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain. j.saez@umh.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Sáez-Valero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018959:CD57 Antigens / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D018959:CD57 Antigens; D002352:Carrier Proteins; D006023:Glycoproteins
keywords: Alzheimer’s disease; Cerebrospinal fluid; Glycoform; Glycoprotein; HNK-1; β-amyloid