Pyroglutamate-Aβ 3 and 11 colocalize in amyloid plaques in Alzheimer's disease cerebral cortex with pyroglutamate-Aβ 11 forming the central core

N-terminal truncated amyloid beta (A beta) derivatives, especially the forms having pyroglutamate at the 3 position (A beta pE3) or at the 11 position (A beta pE11) have become the topic of considerable study. A beta pE3 is known to make up a substantial portion of the A beta species in senile plaques while A beta pE11 has received less attention. We have generated very specific polyclonal antibodies against both species. Each antibody recognizes only the antigen against which it was generated on Western blots and neither recognizes full length A beta. Both anti-A beta pE3 and anti-A beta pE11 stain senile plaques specifically in Alzheimer's disease cerebral cortex and colocalize with A beta, as shown by confocal microscopy. In a majority of plaques examined, A beta pE11 was observed to be the dominant form in the innermost core. These data suggest that A beta pE11 may serve as a generating site for senile plaque formation. Published by Elsevier Ireland Ltd.