Immunohistochemical analysis of COOH-termini of amyloid beta protein (Aβ) using end-specific antisera for Aβ40 and Aβ42 in Alzheimer's disease and normal aging

We examined by immunohistochemicistry the carboxyl (C)-terminus extent of the amyloid beta protein (A beta) that constitutes senile plaques and amyloid angiopathy in the brains of non-demented and Alzheimer's disease (AD) subjects. We developed two antisera, which selectively recognized free C-termini of A beta: BC40 for A beta 40; and BC42 for A beta 42. BC42 labeled various types of senile plaques as well as reference A beta antiserum, whereas only some parts of the senile plaques were positive with BC40: i.e., all of the plaque cores and some diffuse and primitive plaques. In the brains of non-demented middle-aged subjects, a majority of BC42-positive diffuse plaques were also positive with BC40, but with less intensity than that shown with BC42. The ratio of BC40-negative plaques increased with increasing plaque density. Amyloid in the meningeal vessels showed much greater immunoreactivity with BC40 than with BC42. Some extracellular neurofibrillary tangles were positive with both BC40 and BC42, although most of them and all the intraneuronal tangles showed no immunoreactivity with either antiserum. A beta 42 contributed exclusively to senile plaque formation, while contribution of A beta 40 varied among subjects. In vascular amyloid, A beta 40 is an essential component, while A beta 42 showed individual variation.