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Diversity of Senile Plaques in Alzheimers Disease as Revealed by a New Monoclonal Antibody that Recognizes an Internal Sequence of the Aβ Peptide

[ Vol. 2 , Issue. 4 ]

Author(s):

Alberto Rabano, Adolfo Jimenez-Huete, Boris Acevedo, Miguel Calero, Jorge Ghiso, Israel Valdes, Jorge Gavilondo, Blas Frangione and Enrique Mendez   Pages 409 - 417 ( 9 )

Abstract:


In order to have more specific tools available to approach amyloidogenesis in Alzheimers disease (AD), we have produced several polyclonal and monoclonal antibodies that recognize specific sequences of the amyloid β (Aβ) peptide. Here we present results that demonstrate that our monoclonal antibody EM5 recognizes an internal sequence (residues 11-16) of the Aβ 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 AβX-40 and AβX- 42, respectively), in an immunohistochemical study aimed at exploring the differential distribution of longer (AβX- 40/42) and shorter (Aβ17-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 Ab 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 Aβ17-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.

Keywords:

alzheimers disease, amyloid-b, immunohistochemistry, monoclonal antibody, neuritic plaques, amyloid angiopathy, mass spectrometry

Affiliation:

Programa de Neuropatologia, Fundacion Hospital Alcorcon, Avda. de Budapest, 1, 28922 Alcorcon, Madrid, Spain.



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