Diversity of senile plaques in Alzheimer's disease as revealed by a new monoclonal antibody that recognizes an internal sequence of the Abeta peptide.
In order to have more specific tools available to approach amyloidogenesis in Alzheimer's disease (AD), we have produced several polyclonal and monoclonal antibodies that recognize specific sequences of the amyloid beta (Abeta) peptide. Here we present results that demonstrate that our monoclonal antibody EM5 recognizes an internal sequence (residues 11-16) of the Abeta peptide. This strategic localization of the epitope allowed us to employ this antibody, together with two previously reported polyclonal antibodies (EM2 and EM3, specific for AbetaX-40 and AbetaX-42, respectively), in an immunohistochemical study aimed at exploring the differential distribution of longer (AbetaX-40/42) and shorter (Abeta17-X) peptides along the various types of amyloid deposits of AD. This antibody panel was used in six AD brains, on sections from associative neocortex, striatum and cerebellar cortex. Single and double immunostaining revealed specific staining of vascular amyloid deposits and neuritic plaques by EM5 antibody, with high co-localization of EM2. Our results suggest that EM5 antibody recognizes pathogenic forms of Abeta deposits (amyloid angiopathy and neuritic plaques) and reveals the existence of a subset of plaques with a profile similar to vascular deposits. Additionally, our results show that diffuse plaques in AD brains may contain Abeta17-X peptides as its principal component. EM5 may be a useful tool in research both on human and transgenic mice tissue that may aid in the study of molecular heterogeneity of plaques in AD.
Rábano
Alberto
A
Programa de Neuropatología, Fundación Hospital Alcorcón, Avda. de Budapest, 1. 28922 Alcorcón, Madrid, Spain. arabano@fhalcorcon.es
Jiménez-Huete
Adolfo
A
Acevedo
Boris
B
Calero
Miguel
M
Ghiso
Jorge
J
Valdés
Israel
I
Gavilondo
Jorge
J
Frangione
Blas
B
Méndez
Enrique
E
D000544:Alzheimer Disease / Q000473:pathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001923:Brain Chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D058225:Plaque, Amyloid / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments