Leakage and neuronal uptake of serum protein in aged and Alzheimer brains. A postmortem phenomenon with antemortem etiology

Abstract

Abnormal extravasation of serum proteins has frequently been reported in Alzheimer's disease (AD) and less often in nondemented, aged individuals. In order to establish whether these are ante or postmortem phenomena, we have now compared the immunocytochemical localization of immunoglobulin in young, aged, and AD brains. In all the young brains, but only in some of the aged and AD brains, immunoglobulin was confined to a fine network of microvessels. In contrast, the majority of AD, as well as apparently normal, aged brains revealed both focal and diffuse extravascular localization in the form of neuronal labeling as well as a general, diffuse background. Since microvessels in these areas were no longer revealed, it was felt that the extravascular leakage occurred postmortem at a time when replacement of intravascular immunoglobulin had ceased. Furthermore, there was a correlation between the extent of leakage and time interval between death and autopsy. Postmortem leakage of serum protein was reproduced in a more controlled system using young and aged rats; serum protein leakage evolved from focal to diffuse patterns in aged brains as the postmortem period increased, whereas the leakage was restricted to the outer half of the cortices in young brains even after a prolonged postmortem period. Postmortem trauma to the rat brain also caused lesion-related leakage as well as neuronal labeling. It was concluded that extravascular leakage and neuronal uptake in aged and AD brains is a postmortem phenomenon, due to delay in autopsy or mishandling of brains, but dependent in severity upon antemortem circumstances.