Isoform-specific interactions of human apolipoprotein E to an intermediate conformation of human Alzheimer amyloid-beta peptide.
Brain plaque deposits of amyloid-beta peptide (Abeta) is a pathological hallmark of Alzheimer's disease (AD) and apolipoprotein E (apoE) is thought to be involved in its deposition. One hypothesis for the role of apoE in the pathogenesis of AD is that apoE may be involved in deposition or clearance of Abeta by direct protein-to-protein interaction. Lipidated apoE4 bound preferentially to an intermediate aggregated form of Abeta and formed two- to three-fold more binding complexes than isoforms apoE2 or apoE3. The interaction was detected by a sandwich ELISA with capture antibodies specific for the N-terminus of apoE, whereas the interaction was not recognized with a C-terminal antibody. The observations indicate that the C-terminus of apoE4 interacts with the intermediate form of Abeta. The differential risk of AD related to apoE genotype may be the result of an enhanced capacity of apoE4 binding to an intermediate aggregated form of Abeta.
Stratman
Nancy C
NC
Neurobiology, Pfizer Inc., Kalamazoo, MI 49001, USA.
Castle
Christine K
CK
Taylor
Bruce M
BM
Epps
Dennis E
DE
Melchior
George W
GW
Carter
Donald B
DB
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry; D017434:Protein Structure, Tertiary
D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; D020033:Protein Isoforms; C078592:amyloid beta-protein (1-40)