Limited expression of heparan sulphate proteoglycans associated with Aβ deposits in the APPswe/PS1dE9 mouse model for Alzheimer's disease.
OBJECTIVE
Alzheimer's disease (AD) is characterized by deposition of the amyloid beta (Aβ) peptide in brain parenchyma and vasculature. Several proteins co-deposit with Aβ, including heparan sulphate proteoglycans (HSPG). HSPG have been suggested to contribute to Aβ aggregation and deposition, and may influence plaque formation and persistence by stimulating Aβ fibrillization and by protecting Aβ against degradation. Mouse models for AD, expressing the human amyloid precursor protein (APP), produce Aβ deposits similar to humans. These models may be used to study disease pathology and to develop new therapeutic interventions. We aimed to investigate whether co-deposition of HSPG in AD brains can be replicated in the APPswe/PS1dE9 mouse model for AD and if a temporal association of HSPG with Aβ exists.


METHODS
We studied the co-deposition of several HSPG and of the glycosaminoglycan side chains of HSPG in the APPswe/PS1dE9 model at different ages by immunohistochemistry.


RESULTS
We found that, although APPswe/PS1dE9 mice did develop severe Aβ pathology with age, co-deposition of HS glycosaminoglycan chains and the various HSPG (agrin, perlecan and glypican-1) was scarce (<10-30% of the Aβ deposits were stained).


CONCLUSIONS
Our data suggest that the molecular composition of Aβ deposits in the APPswe/PS1dE9 mouse, with respect to the several HSPG investigated in this study, does not accurately reflect the human situation. The near absence of HSPG in Aβ deposits in this transgenic mouse model may, in turn, hinder the translation of preclinical intervention studies from mice to men.
Timmer
N M
NM
Radboud University Nijmegen Medical Centre, Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. n.timmer@neuro.umcn.nl
Herbert
M K
MK
Kleinovink
J W
JW
Kiliaan
A J
AJ
De Waal
R M W
RM
Verbeek
M M
MM
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic
D016229:Amyloid beta-Peptides; D019812:Heparan Sulfate Proteoglycans