Apolipoprotein E is essential for amyloid deposition in the APP V717F transgenic mouse model of Alzheimer's disease
| Autor: | Kelly R. Bales, Steven M. Paul, Josep Saura, Valérie Petegnief, Bernardino Ghetti, Richard C. Dodel, Yansheng Du, Tatyana Verina, Pedro Piccardo, David J. Cummins, Cindy E. Fishman, Cynthia DeLong |
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| Rok vydání: | 1999 |
| Předmět: |
Apolipoprotein E
Genetically modified mouse Amyloid Heterozygote medicine.medical_specialty Transgene Mice Transgenic Hippocampus Apolipoproteins E Amyloid beta-Protein Precursor Mice Alzheimer Disease Internal medicine medicine Amyloid precursor protein Animals Gliosis Cerebral Cortex Mice Knockout Multidisciplinary biology Chemistry Homozygote Brain Biological Sciences medicine.disease Astrogliosis Disease Models Animal Endocrinology biology.protein lipids (amino acids peptides and proteins) Alzheimer's disease medicine.symptom Neuroglia |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:15233-15238 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | We quantified the amount of amyloid β-peptide (Aβ) immunoreactivity as well as amyloid deposits in a large cohort of transgenic mice overexpressing the V717F human amyloid precursor protein ( APP V717F+/− TG mice) with no, one, or two mouse apolipoprotein E ( Apoe ) alleles at various ages. Remarkably, no amyloid deposits were found in any brain region of APP V717F+/− Apoe −/− TG mice as old as 22 mo of age, whereas age-matched APP V717F +/− Apoe +/− and Apoe +/+ TG mice display abundant amyloid deposition. The amount of Aβ immunoreactivity in the hippocampus was also markedly reduced in an Apoe gene dose-dependent manner ( Apoe +/+ > Apoe +/− ≫ Apoe −/− ), and no Aβ immunoreactivity was detected in the cerebral cortex of APP V717F+/− Apoe −/− TG mice at any of the time points examined. The absence of apolipoprotein E protein (apoE) dramatically reduced the amount of both Aβ 1–40 and Aβ 1–42 immunoreactive deposits as well as the resulting astrogliosis and microgliosis normally observed in APP V717F TG mice. ApoE immunoreactivity was detected in a subset of Aβ immunoreactive deposits and in virtually all thioflavine-S-fluorescent amyloid deposits. Because the absence of apoE alters neither the transcription or translation of the APP V717F transgene nor its processing to Aβ peptide(s), we postulate that apoE promotes both the deposition and fibrillization of Aβ, ultimately affecting clearance of protease-resistant Aβ/apoE aggregates. ApoE appears to play an essential role in amyloid deposition in brain, one of the neuropathological hallmarks of Alzheimer's disease. |
| Databáze: | OpenAIRE |
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