Characterization of an O-Glycosylated Plaque-Associated Protein from Alzheimer Disease Brain

Abstract

In this work we characterized a 90-kDa glycoprotein from Alzheimer disease (9OAzgp) brain extracts that is recognized by the GalNAc-specific lectin from Amaranthus leucocarpus (ALL), as determined through Western blot. The 90Azgp was purified by electro-elution, and its amino acid sequence determined from peptides obtained after trypsin digestion through MALDI-TOF (Matrix-assisted laser desorption ionization-time of flight), and compared with the relative values obtained from the NCBInr (Swiss-Prot 10/01/2001) database. The 90Azgp showed 32% and 42% homology with the KIAA0310 protein from human brain and the human gastric mucin, respectively. Presence of O-glycosidically linked glycans in the proteins recognized by ALL was confirmed by inhibition of the lectin-glycoprotein interaction through hapten-inhibition assays and also by elimination of the O-glycosidically linked glycans after treatment with O-glycanase from Diplococcus pneumoniae. Electron transmission microscopy confirmed that the receptor recognized by the lectin is processed in the Golgi apparatus of AD neurons. Although the specific role of this glycoprotein has not been identified, considering that the presence of this lectin receptor co-localized with neuritic plaques and in AD sprouting neurons, it could suggest that the O-glycosyl-protein identified by the A. leucocarpus lectin participates in the pathogenesis of neurodegenerative diseases.

Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias

“…The association of NPs with GALNT7 is novel and potentially reinforces existing genetic associations with other genes that encode for members of this family of transferases. Indeed, alteration in the O-glycosylation pattern of amyloid beta peptides and NPs has been reported in AD [18]–[20]. Finally, we made a novel association of HS with a variant of KCMNB2 , which encodes a subunit of a Ca ++ -gated K + channel that is key to neuronal excitability and is highly expressed by hippocampal pyramidal neurons in sector CA1.…”

Microheterogeneity of some serum glycoproteins in neurodegenerative diseases

“…In AD patients, an increased ratio of the hexasialo-Tf to the less sialylated isoform was detected in the Tf C1 phenotype [28], as well as hyperglycosylated microtubule-associated protein tau [29] or proteins in neural plaques [30]. On the other hand, decreased glycosylation of the regulatory "collapsin response mediator protein 2", associated with neurofibrillary tangles was noted in AD [31].…”

Proteomic profiling of phosphoproteins and glycoproteins responsive to wild-type alpha-synuclein accumulation and aggregation

“…For example, tau proteins in AD brains were abnormally phosphorylated and glycosylated and accumulated as neurofibrillary tangles [5]. The amount of O-glycosylated proteins increased in neuritic plaques and neurofibrillary tangles [6], and the pattern of glycosylation of cholinesterases [7] or transferrin [8] was changed in AD. Therefore, to have a better understanding of the cellular responses to normal or abnormal stimuli, it is important to compare the level, the type and the extent of modifications of a given protein under normal versus diseased states or under different experimental conditions.…”