TY - JOUR
T1 - Biochemical detection of Aβ isoforms
T2 - Implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease
AU - Golde, Todd E.
AU - Eckman, Christopher B.
AU - Younkin, Steven G.
PY - 2000/7/26
Y1 - 2000/7/26
N2 - Prior to the identification of the various abnormal proteins deposited as fibrillar aggregates in the Alzheimer's disease (AD) brain, there was tremendous controversy over the importance of the various lesions with respect to primacy in the pathology of AD. Nevertheless, based on analogy to systemic amyloidosis, many investigators believed that the amyloid deposits in AD played a causal role and that characterization of these deposits would hold the key to understanding this complex disease. Indeed, in retrospect, it was the initial biochemical purifications of the ~4 kDa amyloid β-peptide (Aβ) from amyloid deposits in the mid 1980s that launched a new era of AD research (Glenner and Wong, Biochem. Biophys. Res. Commun. 122 (1984) 1121-1135; Wong et al., Proc. Natl. Acad Sci. USA 82 (1985) 8729-8732; and Masters et al., Proc. Natl. Acad Sci. USA 82 (1985) 4245-4249). Subsequent studies of the biology of Aβ together with genetic studies of AD have all supported the hypothesis that altered Aβ metabolism leading to aggregation plays a causal role in AD. Although there remains controversy as to whether Aβ deposited as classic amyloid or a smaller, aggregated, form causes AD, the relevance of studying the amyloid deposits has certainly been proven. Despite the significant advances in our understanding of the role of Aβ in AD pathogenesis, many important aspects of Aβ biology remain a mystery. This review will highlight those aspects of Aβ biology that have led to our increased understanding of the pathogenesis of AD as well as areas which warrant additional study. Copyright (C) 2000 Elsevier Science B.V.
AB - Prior to the identification of the various abnormal proteins deposited as fibrillar aggregates in the Alzheimer's disease (AD) brain, there was tremendous controversy over the importance of the various lesions with respect to primacy in the pathology of AD. Nevertheless, based on analogy to systemic amyloidosis, many investigators believed that the amyloid deposits in AD played a causal role and that characterization of these deposits would hold the key to understanding this complex disease. Indeed, in retrospect, it was the initial biochemical purifications of the ~4 kDa amyloid β-peptide (Aβ) from amyloid deposits in the mid 1980s that launched a new era of AD research (Glenner and Wong, Biochem. Biophys. Res. Commun. 122 (1984) 1121-1135; Wong et al., Proc. Natl. Acad Sci. USA 82 (1985) 8729-8732; and Masters et al., Proc. Natl. Acad Sci. USA 82 (1985) 4245-4249). Subsequent studies of the biology of Aβ together with genetic studies of AD have all supported the hypothesis that altered Aβ metabolism leading to aggregation plays a causal role in AD. Although there remains controversy as to whether Aβ deposited as classic amyloid or a smaller, aggregated, form causes AD, the relevance of studying the amyloid deposits has certainly been proven. Despite the significant advances in our understanding of the role of Aβ in AD pathogenesis, many important aspects of Aβ biology remain a mystery. This review will highlight those aspects of Aβ biology that have led to our increased understanding of the pathogenesis of AD as well as areas which warrant additional study. Copyright (C) 2000 Elsevier Science B.V.
KW - Alzheimer's disease
KW - Amyloid β protein precursor
KW - Aβ
KW - Biomarker
KW - ELISA
KW - Protease
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U2 - 10.1016/S0925-4439(00)00043-0
DO - 10.1016/S0925-4439(00)00043-0
M3 - Review article
C2 - 10899442
AN - SCOPUS:0034718027
SN - 0925-4439
VL - 1502
SP - 172
EP - 187
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 1
ER -