IMMUNOHISTOCHEMICAL ANALYSIS OF COOH-TERMINI OF AMYLOID-BETA PROTEIN (A-BETA) USING END-SPECIFIC ANTISERA FOR A-BETA-40 AND A-BETA-42 IN ALZHEIMERS-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 d isease (AD) subjects. We developed two antisera, which selectively rec ognized free C-termini of A beta: BC40 for A beta 40; and BC42 for A b eta 42. BC42 labeled various types of senile plaques as well as refere nce A beta antiserum, whereas only some parts of the senile plaques we re positive with BC40: i.e., all of the plaque cores and some diffuse and primitive plaques. In the brains of non-demented middle-aged subje cts, a majority of BC42-positive diffuse plaques were also positive wi th BC40, but with less intensity than that shown with BC42. The ratio of BC40-negative plaques increased with increasing plaque density. Amy loid in the meningeal vessels showed much greater immunoreactivity wit h BC40 than with BC42. Some extracellular neurofibrillary tangles were positive with both BC40 and BC42, although most of them and all the i ntraneuronal tangles showed no immunoreactivity with either antiserum. A beta 42 contributed exclusively to senile plaque formation, while c ontribution of A beta 40 varied among subjects. In vascular amyloid, A beta 40 is an essential component, while A beta 42 showed individual variation.