Alzheimer's paired helical filaments: amyloid precursor protein epitope mapping.
Paired helical filaments (PHF) were electrophoretically purified and solubilized from Alzheimer's neurofibrillary tangles and consisted of a primary 66 kDa protein on SDS-PAGE analysis. A panel of antibodies raised against restricted regions of the beta-amyloid precursor protein (APP) were employed for epitope mapping studies of this 66 kDa PHF protein. Western blot studies revealed that C-terminal APP antibodies were immunoreactive with the 66 kDa PHF protein. Further analysis revealed that only antisera raised against peptides that include the beta/A4-amyloid region within the C-terminal portion of APP were immunoreactive with PHF proteins. These data complement previous immunocytochemical studies which indicated that C-terminal APP antibodies preferentially label PHF-containing neurofibrillary tangles in Alzheimer's brain. The present data suggest a similarity of secondary or tertiary structure between beta/A4-amyloid and PHF which accounts for the cross-reactivity of beta/A4-amyloid antibodies with PHF proteins.
Zemlan
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FP
Alzheimer's Research Center, University of Cincinnati College of Medicine, OH 45267-0559.
Vogelsang
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GD
McLaughlin
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L
Dean
G E
GE
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000302:isolation & purification / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D001931:Brain Mapping; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D000939:Epitopes