text: Miscellaneous Proteins
  Apart from the above-described proteins, several other molecules are also associated with the pathological lesions of AD, and some of these can be regarded as amateur chaperones. Acute phase proteins, such as alpha1-antichymotrypsin (ACT), alpha2-macroglobulin (alpha2M), and SAP, are all associated with Abeta deposition [129-132]. ACT is a serine protease inhibitor of the serpin family, and in AD, ACT levels are upregulated, and binding of ACT with Abeta induces Abeta fibrillogenesis [133-135]. Furthermore, when ACT is overexpressed in transgenic mice, an increased plaque load in the brains of these mice and impaired spatial learning is observed [134, 135]. alpha2M also binds Abeta, although in contrast to ACT, this binding prevents Abeta fibril formation and fibril-associated neurotoxicity [136, 137]. alpha2M promotes the protease-mediated degradation of alpha2M/Abeta complexes and contributes to clearance of Abeta from the brain (discussed in paragraph 4) [138, 139]. The glycoprotein SAP belongs to the pentraxin family and is a common component of all known types of amyloid fibrils. SAP is upregulated in AD and protects amyloid fibrils from proteolysis in vitro [140, 141]. SAP not only colocalizes with SPs and interacts with aggregated Abeta; SAP oligomers also bind and activate C1 [142]. Both C1 and SAP may bind to fibrillar Abeta deposits in vivo and induce microglial activation, as cultured human microglial cells show an increase in cytokine production after co-stimulation of Abeta with C1q and SAP [104]. These observations further strengthen the above-noted suggestion that not only Abeta, but also several Abeta-binding proteins, are capable of activating the complement system, and thus, contribute to neuroinflammation in AD. In addition, both alpha2M and ACT, in contrast to SAP, can be regarded as amateur chaperones, as they regulate conformational changes of Abeta.
  Tissue-type plasminogen activator (tPA) regulates activation of plasminogen into plasmin and is expressed in various regions of the brain especially in the hippocampus [143]. Several reports suggested an important role for tPA in AD, as the tPA system is involved in Abeta turnover [144, 145]. Fibrillar forms of Abeta stimulate tPA activity in vitro, whereas in AD patients, a reduction of tPA activity is observed in the affected areas [144, 146]. Although tPA has no effect on conformational changes of Abeta, it might play a role in the clearance of Abeta from the brain (paragraph 4].
  The actin-regulatory protein gelsolin is found both intracellularly and in plasma [147, 148]. Plasma gelsolin can be considered an amateur chaperone, as it binds Abeta and not only inhibits its Abeta fibrillization but is also capable of degrading preformed Abeta fibrils [149, 150]. Furthermore, gelsolin inhibits Abeta-mediated neurotoxicity [151].
  One of the major gangliosides in the brain is GM1. Soluble Abeta binds GM1 and the formed complexes accelerate Abeta fibrillogenesis by acting as a seed for Abeta [152]. In the presence of GM1, Abeta is more neurotoxic than Abeta alone, and cholesterol-rich membranes demonstrate accelerated Abeta binding due to the formation of GM1 clusters [153, 154]. As GM1 is a major component of lipid rafts and recent studies suggest that Abeta accumulation in these lipid rafts is an early event in AD development, GM1 might play an important role in the early steps in AD pathogenesis [155, 156].
  In summary, several proteins are associated with Abeta aggregates in the AD brain and contribute to the aggregation of Abeta and should, therefore, be considered as amateur chaperones. In addition, they might play a role in triggering inflammation.
  
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