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Apolipoprotein E, Plaques, Tangles and Cholinergic Dysfunction in Alzheimer's Disease a
Author(s) -
BEFFERT U.,
POIRIER J.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb34415.x
Subject(s) - senile plaques , apolipoprotein e , choline acetyltransferase , alzheimer's disease , tau protein , neurofibrillary tangle , hippocampal formation , cholinergic , population , apolipoprotein b , amyloid beta , biology , endocrinology , neuroscience , medicine , cholesterol , disease , environmental health
Apolipoprotein E is a plasma cholesterol and phospholipid transporter which plays a central role in lipoprotein metabolism in the brain. Apolipoprotein E is a polymorphic protein with three common alleles in the general population, designated ε2, ε3 and ε4 coding for proteins ApoE2, ApoE3 and ApoE4, respectively. Recent findings have demonstrated a significant relationship between the ε4 allele and late onset familial and sporadic Alzheimer's disease. We examined several classical neuropathological hallmarks of Alzheimer's disease to determine whether they might be related to apolipoprotein E genotype: the presence of intracellular neurofibrillary tangles, extracellular senile plaques, and the attenuation of choline acetyltransferase activity. Significant correlations were found between ε4 allele copy number and senile plaque density in the frontal, parietal and fusiform cortical areas. Similarly, significant correlations were also found with increased neurofibrillary tangle number in the frontal and fusiform cortex. Interestingly, there was an inverse correlation between the ε4 allele with temporal cortical choline acetyltransferase activity. To further define the specific function of ApoE4, cultured rat hippocampal neurons were used to investigate interactions involving β‐amyloid protein. In this model, ApoE4 (but not ApoE2) was able to reverse the neuroprotective effects of β‐amyloid. ApoE3 was demonstrated to increase the internalization of β‐amyloid peptide into these neurons. Taken together, these results support the involvement of ApoE4 in the pathogenesis of Alzheimer's disease and also provide some explanations for the possible function of this protein.