Overexpression of human apolipoprotein B-100 induces severe neurodegeneration in transgenic mice.
Recent studies showed correlation between increased serum apolipoprotein B-100 (apoB-100) level and Alzheimer's disease. To reveal the possible role of apoB-100 in neurodegeneration, we analyzed the serum lipoprotein and cerebral protein profiles, amyloid plaque formation, apoptosis and brain morphology of transgenic mice overexpressing the human apoB-100 protein. Serum lipoprotein profile showed significant increase of the plasma triglyceride level, while no alteration in total cholesterol was detected. The antibody microarray experiment revealed upregulation of several cytoskeletal, neuronal proteins and proteins that belong to the mitogen activated protein kinase pathway, indicating active apoptosis in the brain. Histochemical experiments showed formation of amyloid plaques and extensive neuronal death. Biochemical changes severely affected brain morphology; a dramatic genotype-dependent enlargement of the third and lateral ventricles in the brain was detected. On the basis of earlier and present results, we conclude that overexpressed human apoB-100 protein significantly increases the level of serum lipids (triglyceride upon normal chow diet and cholesterol on cholesterol-rich diet) which leads to cerebrovascular lesions and subsequently induces apoptosis and neurodegeneration.
Bereczki
Erika
E
Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 521, H-6701 Szeged, Hungary.
Bernát
Gábor
G
Csont
Tamás
T
Ferdinandy
Péter
P
Scheich
Henning
H
Sántha
Miklós
M
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D053299:Apolipoprotein B-100 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D040081:Protein Array Analysis; D014280:Triglycerides / Q000097:blood
D016564:Amyloid beta-Protein Precursor; D053299:Apolipoprotein B-100; D002791:Cholesterol, Dietary; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D014280:Triglycerides; D002784:Cholesterol