Colocalization of amino terminal and A4 (beta-amyloid) antigens in Alzheimer plaques: evidence for coordinated processing of the amyloid precursor protein.

The mechanism by which the A4 (beta-amyloid) domain of the Alzheimer amyloid precursor protein (APP) is deposited in plaques is unknown, and limited information is available concerning the extent to which other APP sites are associated with plaques. To address these issues, we prepared antiserum to a peptide adjacent to the N-terminus of the APP (referred to as N1) and examined its distribution in brain relative to A4 by double-immunostaining techniques. Anti-N1 localized to both neurons and glia in control and Alzheimer patients. In the Alzheimer brain, anti-N1 detected plaques. Quantitation revealed that 85% of thioflavin-positive plaques, and 91% of A4-positive plaques were also N1 positive. Double-staining methods directly demonstrated colocalization of distant APP sites. The data suggest that suggest that proposed mechanisms for amyloid deposition during plaque formation must take into account the extracytoplasmic domain, in addition to the A4 region, rather than be confined exclusively to the A4 site.