In humans, the apolipoprotein E gene (APOE) is polymorphic with the alleles APOE ϵ2, 3 and 4 coding for apolipoproteins (Apo) E2, 3 and 4. Apart from age, the APOE ϵ4 allele represents the most important risk factor in sporadic Alzheimer's disease (AD). Compared to APOE ϵ3 homozygotes, the histopathological onset of tau pathology is found 1-2 decades earlier but progresses with the same speed. ApoE dose-dependently and specifically increases free intraneuronal calcium levels in the order ApoE4 > ApoE3 > ApoE2. This effect is amplified in the presence of ϐA4-peptide. The ApoE effects on calcium are not affected by the blockade of action potentials with tetrodotoxin, or by inhibition of common ApoE binding sites. The calcium channel involved has been identified as a P/Q-type-like channel. Brain tissue ApoE levels differ with respect to APOE alleles and Braak-stage for Alzheimer-histopathology. The production of ApoE in astrocytes is controlled by several receptor/effector systems such as adrenoceptors and cAMP. In the presence of ϐA4-peptide fragments, astrocytes stop their synthesis of ApoE resulting in a massive reduction in the bioavailability of ApoE. In the periphery, ApoE directs cholesterol transport and thereby influences its cellular concentrations. In neurons, changes in the concentration of cholesterol influence the phosphorylation status of the microtubule-associated protein tau at sites known to be altered in AD.
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February 2001
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February 01 2001
Apolipoprotein E and ϐA4-amyloid: signals and effects
Thomas G. Ohm;
Thomas G. Ohm
1
*Institute fur Anatomie, University Klinikum Charité, D-10098 Berlin, Germany.
1To whom correspondence should be addressed.
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Ulrike Hamker;
Ulrike Hamker
*Institute fur Anatomie, University Klinikum Charité, D-10098 Berlin, Germany.
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Angel Cedazo-Minguez;
Angel Cedazo-Minguez
†Department of Clinical Neuroscience, Div. Geriatric Medicine, Karolinska, 14186 Huddinge, Sweden.
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Wolfgang Röckl;
Wolfgang Röckl
*Institute fur Anatomie, University Klinikum Charité, D-10098 Berlin, Germany.
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Hubert Scharnagl;
Hubert Scharnagl
‡Department of Clinical Chemistry, Albert-Ludwigs-University, D-79106 Freiburg, Germany.
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Winfried März;
Winfried März
‡Department of Clinical Chemistry, Albert-Ludwigs-University, D-79106 Freiburg, Germany.
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Richard Cowburn;
Richard Cowburn
†Department of Clinical Neuroscience, Div. Geriatric Medicine, Karolinska, 14186 Huddinge, Sweden.
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Wolfgang Müller;
Wolfgang Müller
§Institute of Physiology, University Klinikum Charité, D-10098 Berlin, Germany.
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Volker Meske
Volker Meske
*Institute fur Anatomie, University Klinikum Charité, D-10098 Berlin, Germany.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 2001 The Biochemical Society
2001
Biochem Soc Symp (2001) 67: 121–129.
Citation
Cora O'Neill, Brian Anderton, Thomas G. Ohm, Ulrike Hamker, Angel Cedazo-Minguez, Wolfgang Röckl, Hubert Scharnagl, Winfried März, Richard Cowburn, Wolfgang Müller, Volker Meske; Apolipoprotein E and ϐA4-amyloid: signals and effects. Biochem Soc Symp 1 February 2001; 67 121–129. doi: https://doi.org/10.1042/bss0670121
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