Heparan sulphate proteoglycans in Alzheimer's disease and amyloid‐related disorders

J Van Horssen, P Wesseling… - The Lancet …, 2003 - thelancet.com
J Van Horssen, P Wesseling, LPWJ Van Den Heuvel, RMW De Waal, MM Verbeek
The Lancet Neurology, 2003thelancet.com
Proteoglycans are associated with all kinds of amyloid deposits in the human body. These
complex macromolecules, in particular heparan sulphate proteoglycans, have also been
implicated in several features of the pathogenesis of Alzheimer's disease (AD), including the
genesis of senile plaques, cerebrovascular amyloid, and neurofibrillary tangles. In this
review we focus on the role of proteoglycans and glycosaminoglycans in amyloidogenesis
in general and in AD in particular. Heparan sulphate proteoglycans may promote amyloid-β …
Summary
Proteoglycans are associated with all kinds of amyloid deposits in the human body. These complex macromolecules, in particular heparan sulphate proteoglycans, have also been implicated in several features of the pathogenesis of Alzheimer's disease (AD), including the genesis of senile plaques, cerebrovascular amyloid, and neurofibrillary tangles. In this review we focus on the role of proteoglycans and glycosaminoglycans in amyloidogenesis in general and in AD in particular. Heparan sulphate proteoglycans may promote amyloid-β peptide (Aβ) or tau fibrillisation on the one hand, and provide resistance against proteolytic breakdown on the other. Knowledge about the role of proteoglycans in AD pathology may eventually be of therapeutic use, because small polysulphated compounds, which can interfere with the interaction between proteoglycan and Aβ, have been shown to stop or even prevent amyloidogenesis.
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