TY - JOUR
T1 - Molecular chaperons, amyloid and preamyloid lesions in the BRI2 gene-related dementias
T2 - a morphological study
AU - Lashley, T
AU - Holton, J L
AU - Verbeek, M M
AU - Rostagno, A
AU - Bojsen-Møller, M
AU - David, G
AU - van Horssen, J
AU - Braendgaard, H
AU - Plant, G
AU - Frangione, B
AU - Ghiso, J
AU - Revesz, T
PY - 2006/10
Y1 - 2006/10
N2 - 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 in4 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.
AB - 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 in4 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.
KW - Alzheimer Disease/genetics
KW - Amyloid/genetics
KW - Amyloid Neuropathies/pathology
KW - Apolipoproteins E/genetics
KW - Dementia/genetics
KW - Heparan Sulfate Proteoglycans/metabolism
KW - Heparitin Sulfate/metabolism
KW - Humans
KW - Immunohistochemistry
KW - Membrane Glycoproteins/metabolism
KW - Molecular Chaperones/metabolism
KW - Nerve Tissue Proteins/genetics
KW - Protein Conformation
KW - Proteoglycans/metabolism
KW - Serum Amyloid P-Component/metabolism
KW - Syndecans
KW - alpha 1-Antichymotrypsin/metabolism
U2 - 10.1111/j.1365-2990.2006.00747.x
DO - 10.1111/j.1365-2990.2006.00747.x
M3 - Article
C2 - 16972883
VL - 32
SP - 492
EP - 504
JO - Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
SN - 0305-1846
IS - 5
ER -