Differential recognition of vascular and parenchymal beta amyloid deposition.
By phage display, llama-derived heavy chain antibody fragments were selected from non-immune and immune libraries and tested for their affinity and specificity for beta amyloid by phage-ELISA, immunohistochemistry and surface plasmon resonance. We identified eight distinct heavy chain antibody fragments specific for beta amyloid. While three of them recognized vascular and parenchymal beta amyloid deposits, the remaining five heavy chain antibody fragments recognized vascular beta amyloid specifically, failing to bind to parenchymal beta amyloid. These heavy chain antibody fragments, selected from different libraries, demonstrated differential affinity for different epitopes when used for immunohistochemistry. These observations indicate that the llama heavy chain antibody fragments are the first immunologic probes with the ability to differentiate between parenchymal and vascular beta amyloid aggregates. This indicates that vascular and parenchymal beta amyloid deposits are heterogeneous in epitope presence/availability. The properties of these heavy chain antibody fragments make them potential candidates for use in in vivo differential diagnosis of Alzheimer disease and cerebral amyloid angiopathy. Continued use and characterization of these reagents will be necessary to fully understand the performance of these immunoreagents.
Rutgers
Kim S
KS
Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
van Remoortere
Alexandra
A
van Buchem
Mark A
MA
Verrips
C Theo
CT
Greenberg
Steven M
SM
Bacskai
Brian J
BJ
Frosch
Matthew P
MP
van Duinen
Sjoerd G
SG
Maat-Schieman
Marion L
ML
van der Maarel
Silvère M
SM
D000544:Alzheimer Disease / Q000473:pathology; D000682:Amyloid / Q000276:immunology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology; D028243:Cerebral Amyloid Angiopathy, Familial / Q000378:metabolism / Q000473:pathology; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D019151:Peptide Library; D012680:Sensitivity and Specificity; D020349:Surface Plasmon Resonance / Q000379:methods
D000682:Amyloid; D016229:Amyloid beta-Peptides; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D019151:Peptide Library