Molecular chaperons, amyloid and preamyloid lesions in the BRI2 gene-related dementias: a morphological study
(2006) Neuropathology and Applied Neurobiology — Vol. 32, n° 5, p. 492-504 (2006)
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- Molecular chaperons or amyloid-associated proteins (AAPs) are deposited in vascular and parenchymal amyloid lesions in Alzheimer's disease (AD) and other amyloidoses. AAPs, such as apolipoprotein E (ApoE) or apolipoprotein J (ApoJ) have been strongly implicated in the pathogenesis of AD in vitro and in vivo. Furthermore the possession of the ApoE is an element of 4 allele is a well-studied risk factor for AD. In view of the similarities between AD and both familial British dementia (FBD) and familial Danish dementia (FDD), we investigated the presence of AAPs in these two diseases to understand better their role in the general process of amyloidogenesis. Immunohistochemistry for ApoE, ApoJ, serum amyloid P (SAP), alpha-1-antichymotrypsin, cystatin C, heparan sulphate proteoglycans, such as agrin, perlecan, syndecans, glypican-1 and for heparan sulphate glycosaminoglycan (HS GAG) side chains was carried out together with immunohistochemical preparations specific to the amyloid subunits. Significant or extensive staining for ApoE, ApoJ, agrin, glypican-1 and HS GAG side chains was found in both amyloid (fibrillar) and preamyloid (nonfibrillar) deposits in FBD and FDD. The remaining AAPs, including SAP, were predominantly found in amyloid lesions. Only very weak staining was present in a small proportion of the amyloid lesions using perlecan immunohistochemistry. These findings suggest that the deposition patterns of AAPs in FBD and FDD are mostly similar to those in AD. The presence of AAPs in the preamyloid lesions supports the notion that chaperon molecules may play a role in the early steps of fibrillogenesis.
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Lashley, T., Holton, J. L., Verbeek, M. M., Rostagno, A., Bojsen-Moller, M., David, G., van Horssen, J., Braendgaard, H., Plant, G., Frangione, B., Ghiso, J., & Revesz, T. (2006). Molecular chaperons, amyloid and preamyloid lesions in the BRI2 gene-related dementias: a morphological study. Neuropathology and Applied Neurobiology, 32(5), 492-504. https://doi.org/10.1111/j.1365-2990.2006.00747.x (Original work published 2006)