Pyroglutamate-AI super(2) 3 and 11 colocalize in amyloid plaques in Alzheimer's disease cerebral cortex with pyroglutamate-AI super(2) 11 forming the central core

N-terminal truncated amyloid beta (AI super(2)) derivatives, especially the forms having pyroglutamate at the 3 position (AI super(2)pE3) or at the 11 position (AI super(2)pE11) have become the topic of considerable study. AI super(2)pE3 is known to make up a substantial portion of the AI super(2) species in senile plaques while AI super(2)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 AI super(2). Both anti-AI super(2)pE3 and anti-AI super(2)pE11 stain senile plaques specifically in Alzheimer's disease cerebral cortex and colocalize with AI super(2), as shown by confocal microscopy. In a majority of plaques examined, AI super(2)pE11 was observed to be the dominant form in the innermost core. These data suggest that AI super(2)pE11 may serve as a generating site for senile plaque formation.