A quantitative and immunohistochemical study on apolipoprotein E in brain 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 interaction between ApoE and beta-amyloid has been found in in vitro studies. Further, an increased frequency of the ApoE epsilon4 allele in AD has been reported in numerous papers. However, the pathogenetic mechanism of ApoE in AD is not known. We studied ApoE in brain tissue (hippocampus, cerebellum, frontal and temporal cortex) from patients with AD and age-matched control subjects, using both quantitative Western blotting and immunohistochemistry. In AD, a reduction of ApoE was found in the hippocampus (50% of the control value) and in the frontal cortex (52% of the control value), while no significant changes in ApoE levels were found in the temporal cortex or in the cerebellum. Also by immunohistochemistry, ApoE staining was generally decreased in AD brains, both in the neuropil and in the neuronal cellular compartments. 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 cortex (r = -0.03 and r = 0.01, respectively). There were no significant differences in duration, severity of dementia, SP or NFT counts, or ApoE levels between AD patients with different numbers of ApoE epsilon4 alleles. After experimental brain damage in animals, marked increases in ApoE are found, probably 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, beta-amyloid deposition and NFT formation. Copyrightz1999S.KargerAG,Basel
Hesse
C
C
Department of Clinical Neuroscience, Unit of Neurochemistry, University of Göteborg, Sahlgren's University Hospital, Mölndal, Sweden. camilla.hesse@ms.se
Bogdanovic
N
N
Davidsson
P
P
Blennow
K
K
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology; D001057:Apolipoproteins E / Q000378:metabolism*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology
D001057:Apolipoproteins E