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Halim A, Brinkmalm G, Rüetschi U, Westman-Brinkmalm A, Portelius E, Zetterberg H, Blennow K, Larson G, Nilsson J. Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein/amyloid beta-peptides in human cerebrospinal fluid. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11848-53. PubMed.
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Comments
Washington University School of Medicine
This is an interesting article to read, and the supporting documents contain a wealth of information about the reported findings. Tyrosine O-glycosylation is unusual, but the data demonstrated clearly that it actually occurred in this instance. The authors characterized the glycosylation sites of amyloid precursor proteins (APP) and amyloid β (Aβ) for the first time, and the data they provided demonstrated that clearly. It is interesting that Tyr10 O-glycosylation was not identified in APP, but was identified in shorter N-terminal Aβ1-X, with X equal to or less than 20.
Meanwhile, the same Tyr10 O-glycosylation was not identified in all of the full-length Aβ isoforms. I wish the authors had showed how they came up with a scale of the heat map for the spectral relative intensities of peptide glycosylation. I was wondering if the scale was done with calibration peptide standards, or if it was based solely on the response of the mass spectrometer used in the study.
Anyhow, the heat map seemed to illustrate the difference in intensities of peptides with Tyr10 O-glycosylation compared with those without it. The finding does suggest that Tyr10 O-glycosylation occurred primarily in samples obtained in Alzheimer's disease (AD) patients; however, data from at least one of the non-AD patients also showed increased Tyr10 O-glycosylation. The borderline of who has AD, and who has not, was not clear according to the findings. Relying on the 530 pg/ml Aβ1-42 concentration was insufficient to separate the patient population as stated in this article or the 500 pg/ml that was reported elsewhere (1). Unfortunately, the shortcoming of this study is that the sample size was limited, and a deviation of one out of six non-AD patient results becomes statistically significant.
References:
Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan AM, Morris JC, Mawuenyega KG, Cruchaga C, Goate AM, Bales KR, Paul SM, Bateman RJ, Holtzman DM. Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci Transl Med. 2011 Jun 29;3(89):89ra57. PubMed.
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