A quantitative and immunohistochemical study on apolipoprotein E in grain tissue in Alzheimer's disease

Apoliprotein E (ApoE) has been implicated in the pathogenesis of Alzheimer' s disease (AD). Antibodies to ApoE label senile plaques (SP), and an intera ction between ApoE and beta-amyloid has been found in in vitro studies. Fur ther, an increased frequency of the ApoE epsilon 4 allele in AD has been re ported in numerous papers. However, the pathogenetic mechanism of ApoE in A D is not known. We studied ApoE in brain tissue (hippocampus, cerebellum, f rontal and temporal cortex) from patients with AD and age-matched control s ubjects, using both quantitative Western blotting and immunohistochemistry. In AD, a reduction of ApoE was found in the hippocampus (50% of the contro l value) and in the frontal cortex (52% of the control value), while no sig nificant changes in ApoE levels were found in the temporal cortex or in the cerebellum. Also by immunohistochemistry, ApoE staining was generally decr eased in AD brains, both in the neuropil and in the neuronal cellular compa rtments. Within the AD group, there was no significant correlation between the ApoE level and SP or neurofibrillary tangle (NFT) counts, either in the hippocampus (r = -0.14 and r = 0.55, respectively), or in the frontal cort ex (r = -0.03 and r = 0.01, respectively). There were no significant differ ences in duration, severity of dementia, SP or NFT counts, or ApoE levels b etween AD patients with different numbers of ApoE epsilon 4 alleles. After experimental brain damage in animals, marked increases in ApoE are found, p robably as part of lipid recycling in neuronal and synaptic remodelling and regeneration. One may speculate whether the decrease in ApoE may suggest a disturbance in the ApoE system in AD that is unrelated to ApoE isoforms, b eta-amyioid deposition and NFT formation. Copyright (C) 1999 S. Karger AG, Basel.