Identification of cellular and extracellular sites of amyloid precursor protein extracytoplasmic domain in normal and Alzheimer disease brains.

Information concerning the distribution of various subdomains of the amyloid precursor protein (APP) in brain may illuminate aspects of the normal metabolism of this membrane-associated protein, as well as putative abnormal processing that may occur in Alzheimer disease (AD). We prepared affinity-purified antibody, P2, against an extracytoplasmic APP site and applied it, along with monoclonal antibodies to the beta-peptide, or A4 region, in conjunction with selective cytochemical staining methods, to control and AD tissues. The following was noted: (i) in contrast to A4 epitopes, which are easily demonstrable primarily in extracellular senile plaques of AD patients, the extracytoplasmic P2 antigen was found in association with neurons, glia, and blood vessels in both normal and AD prefrontal cortex; (ii) a subset of senile plaques contained both A4 and P2 antigens; (iii) in some instances, P2 antigen occurred as an extracellular deposit in the absence of A4; (iv) the P2 antigen, but not A4, was also associated with corpora amylacea. In addition to identifying the unique cellular distribution of the APP extracytoplasmic antigen, the results support the view that a segment of this domain undergoes processing and deposition at extracellular sites, including a subset of senile plaques.