Journal
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
Volume 36, Issue 6, Pages 478-486Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2990.2010.01091.x
Keywords
Alzheimer's disease; amyloid beta; heparan sulphate proteoglycans; transgenic mice
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Funding
- Internationale Stichting Alzheimer Onderzoek (ISAO) [07510]
- Netherlands Organization for Scientific Research (NWO/ZonMW) [917.46.331]
- Hersenstichting Nederland [14F06.18]
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Aims: Alzheimer's disease (AD) is characterized by deposition of the amyloid beta (A beta) peptide in brain parenchyma and vasculature. Several proteins co-deposit with A beta, including heparan sulphate proteoglycans (HSPG). HSPG have been suggested to contribute to A beta aggregation and deposition, and may influence plaque formation and persistence by stimulating A beta fibrillization and by protecting A beta against degradation. Mouse models for AD, expressing the human amyloid precursor protein (APP), produce A beta 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 A beta 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 A beta pathology with age, co-deposition of HS glycosaminoglycan chains and the various HSPG (agrin, perlecan and glypican-1) was scarce (< 10-30% of the A beta deposits were stained). Conclusions: Our data suggest that the molecular composition of A beta 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 A beta deposits in this transgenic mouse model may, in turn, hinder the translation of preclinical intervention studies from mice to men.
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