HNK-1 Carrier Glycoproteins Are Decreased in the Alzheimer’s Disease Brain

• Published in: Molecular neurobiology Vol. 54; no. 1; pp. 188 - 199
• Main Authors: García-Ayllón, María-Salud, Botella-López, Arancha, Cuchillo-Ibañez, Inmaculada, Rábano, Alberto, Andreasen, Niels, Blennow, Kaj, Ávila, Jesús, Sáez-Valero, Javier
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2017; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amino Acid Sequence; Animals; Biomedical and Life Sciences; Biomedicine; Brain; Brain - metabolism; Brain - pathology; Carrier Proteins - genetics; Carrier Proteins - metabolism; CD57 Antigens - genetics; CD57 Antigens - metabolism; Cell Biology; Cell Line, Tumor; Enzymes; Female; Glycoproteins - genetics; Glycoproteins - metabolism; Humans; Longitudinal Studies; Male; Medicin och hälsovetenskap; Mice; Mice, Transgenic; Neurobiology; Neurology; Neurosciences; Neurovetenskaper; Proteins; HNK-1; Glycoform; Cerebrospinal fluid; Alzheimer’s disease; Glycoprotein; β-amyloid
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-015-9644-x

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.