Distribution of apolipoprotein E in senile plaques in brains with Alzheimer's disease: investigation with the confocal laser scan microscope.

In order to elucidate the mechanism of the occurrence of apolipoprotein E (ApoE) in senile plaques (SP) in the brain of Alzheimer's disease (AD) patients, we morphologically examined double immunofluorescent-stained sections by scanning with the confocal laser scan microscope (LSM) and reconstructed their three-dimensional structure by a computerized imaging technique. Brain samples were obtained from six pathologically diagnosed AD patients, including patients with the genotype ApoE epsilon 3/3 and epsilon 4/4 ApoE genotype. We found some clear differences in distribution and shape in the staining patterns of plaque-shaped deposits by ApoE antibody and amyloid beta-protein (A beta) antibody. ApoE deposits were generally larger than A beta deposits in the same region and were distributed widely at the periphery of A beta deposits. Several A beta deposits of typical, compact and primitive plaques were often included in one diffuse plaque-like deposit of ApoE. Some ApoE deposits did not exhibit any A beta-immunoreactivity. Each core represented by ApoE and A beta did not show complete overlap. Typical plaques tended to be composed mainly of A beta-immunoreactivity and had little ApoE-immunoreactivity. The discrepancy between ApoE and A beta deposition may reflect different stages of amyloidogenesis in SP. The presence of ApoE alone in plaques may represent the pathological stage before the beginning of massive A beta deposition.