In contrast, ECM components such as heparan sulfate proteoglycans (HSPGs) direct the binding and regulate the internalization of misfolded assemblies like PrP [92] and tau [93] or Aβ [94], for which HSPGs act promoting also the conversion of non-fibrillar Aβ into neurotoxic fibrillar forms in AD. Here, PRNP is linked to Alzheimer disease.