Antibodies directed to the carboxyl terminus of amyloid beta-peptide recognize sequence epitopes and distinct immunoreactive deposits in Alzheimer's disease brain

Amyloid P-peptide (AB) deposits in Alzheimer disease (AD) are composed of s pecies with heterogeneous N- and C-termini. The availability of antibodies selective for the different AP variants represents a major advance in the i nvestigation of AP amyloidogenesis. The precise characterization of these a ntibodies is essential to allow valid interpretation of the data. To furthe r analyze this subject, EMI, EM2, EM3 and EM4 polyclonal antibodies were ra ised against A beta(1-42), A beta(1-40), A beta(37-42) and A beta(37-40) sy nthetic peptides. As shown by ELISA, immunoblot analysis and inhibition ass ays, EM2 and EM3 presented a selective recognition of A beta(x-40) and A be ta(x-42) variants, respectively This recognition was not dependent on the s econdary structure of the AP peptides, indicating that EM2 and EM3 antisera react with sequence epitopes. Immunohistochemical studies using EM2 and EM 3 confirm previous reports on the differential distribution of A beta(x-40) and A beta(x-42) species in AD brains. While A beta(x-40) deposits were re stricted mainly to cored plaques and arterial vessels, A beta(x-42) peptide s were found In preamyloid lesions, cored and uncored plaques, and arterial and capillary vessels. The mechanisms underlying these differences are unk nown, but local divergences in the processing of either the amyloid precurs or protein or A beta(x-42(43)) species may be important.