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BioMed Research International
Volume 2014 (2014), Article ID 516028, 9 pages
http://dx.doi.org/10.1155/2014/516028
Review Article

Towards Understanding the Roles of Heparan Sulfate Proteoglycans in Alzheimer’s Disease

1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
2Department of Neuroscience, Pharmacology, University of Uppsala, The Biomedical Center, 751 23 Uppsala, Sweden
3Department of Medical Biochemistry and Microbiology, University of Uppsala, The Biomedical Center, 751 23 Uppsala, Sweden

Received 3 May 2014; Accepted 12 July 2014; Published 23 July 2014

Academic Editor: Ilona Kovalszky

Copyright © 2014 Gan-lin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Alzheimer’s disease (AD) is the most common form of dementia, characterized by progressive loss of memory and cognitive dysfunctions. A central pathological event of AD is accumulation and deposition of cytotoxic amyloid-β peptide (Aβ) in the brain parenchyma. Heparan sulfate proteoglycans (HSPGs) and the side chains heparan sulfate (HS) are found associated with Aβ deposits in the brains of AD patients and transgenic animal models of AD. A growing body of evidence from in vitro and in vivo studies suggests functional roles of HSPG/HS in Aβ pathogenesis. Although the question of “how and why HSPG/HS is codeposited with Aβ?” still remains, it is within reach to understand the mechanisms of the events. Recent progress by immunohistochemical examination with advanced antibodies shed light on molecular structures of HS codeposited with Aβ. Several recent reports have provided important new insights into the roles of HSPG in Aβ pathogenesis. Particularly, experiments on mouse models revealed indispensible functions of HSPG in modulating Aβ-associated neuroinflammation and clearance of Aβ from the brain. Application of molecules to interfere with the interaction between HS and Aβ peptides has demonstrated beneficial effects on AD mouse models. Elucidating the functions of HSPG/HS in Aβ deposition and toxicity is leading to further understanding of the complex pathology of AD. The progress is encouraging development of new treatments for AD by targeting HS-Aβ interactions.