Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease
| Autor: | Maia Parsadanian, David F. Wozniak, Tanya Tenkova, David M. Holtzman, Brian Mackey, Steven M. Paul, Anne M. Fagan, John W. Olney, Daniel W. McKeel, Leah J. Sartorius, Kelly R. Bales |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Time Factors Neurite Transgene Mice Transgenic Plaque Amyloid Biology Hippocampus Apolipoproteins E Pathogenesis Mice Alzheimer Disease Internal medicine Neurites medicine Animals Humans Protein Isoforms Hippocampus (mythology) Genetic Predisposition to Disease Benzothiazoles Senile plaques Multidisciplinary Biological Sciences medicine.disease Mice Inbred C57BL Disease Models Animal Thiazoles Endocrinology Mice Inbred DBA Nerve Degeneration lipids (amino acids peptides and proteins) Alzheimer's disease |
| Zdroj: | Proceedings of the National Academy of Sciences. 97:2892-2897 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.050004797 |
| Popis: | Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ɛ4 > ɛ3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-β (Aβ) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Aβ deposition and AD pathology, we compared APP V717F transgenic (TG) mice expressing mouse, human, or no apoE (apoE −/− ). A severe, plaque-associated neuritic dystrophy developed in APP V717F TG mice expressing mouse or human apoE. Though significant levels of Aβ deposition also occurred in APP V717F TG, apoE −/− mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP V717F TG, apoE −/− mice resulted in fibrillar Aβ deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP V717F TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|