Altered glycosylation of acetylcholinesterase in APP (SW) Tg2576 transgenic mice occurs prior to amyloid plaque deposition.
Previous studies have shown that a minor glycoform of acetylcholinesterase (AChE) is increased in Alzheimer's disease brain and cerebrospinal fluid. This glycoform can be distinguished from other AChE species by its lack of binding to concanavalin A (Con A). In this study, the temporal relationship between AChE glycosylation and Abeta deposition was examined in Tg2576 mice. There was a significant (p < 0.05) difference in AChE glycosylation in Tg2576 mice compared with age-matched background strain control mice at 4 months of age. This difference in glycosylation was also observed in 8- and 12-month-old Tg2576 mice. In contrast, Abeta plaques were only seen in the Tg2576 mice at 12 months of age, and were not detected at 4 and 8 months of age. Soluble human-sequence Abeta was detected as early as 4 months of age in the transgenic mice. The altered AChE glycosylation was due to an increase in a minor AChE isoform, which did not bind Con A, similar to that previously observed to be increased in Alzheimer's disease brain and cerebrospinal fluid. The results demonstrate that in transgenic mice altered AChE glycosylation is associated with very early events in the development of AD-like pathology. The study supports the possibility that glycosylation may also be a useful biomarker of AD.
Fodero
Lisa R
LR
Laboratory of Molecular Neurobiology, Department of Pathology, The University of Melbourne, Melbourne, Australia.
Sáez-Valero
Javier
J
McLean
Catriona A
CA
Martins
Ralph N
RN
Beyreuther
Konrad
K
Masters
Colin L
CL
Robertson
Terry A
TA
Small
David H
DH
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006031:Glycosylation; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D000110:Acetylcholinesterase