Apolipoprotein E influences amyloid-beta clearance from the murine periphery
| Autor: | Ralph N. Martins, Eugene Hone, Justin Fonte, Ian Martins |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Gene isoform
Apolipoprotein E medicine.medical_specialty Time Factors Metabolic Clearance Rate Amyloid beta Blotting Western Kidney Mice Apolipoproteins E Western blot Alzheimer Disease In vivo Internal medicine mental disorders medicine Animals Protein precursor Mice Knockout Amyloid beta-Peptides biology medicine.diagnostic_test Chemistry General Neuroscience General Medicine In vitro nervous system diseases Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health Clinical Psychology Endocrinology Liver Cell culture biology.protein Geriatrics and Gerontology |
| Zdroj: | Europe PubMed Central Macquarie University |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-2003-5101 |
| Popis: | The relationship between amyloid-beta protein (Abeta) metabolism and Alzheimer's disease is currently poorly understood. While it is well known that the generation of Abeta results from enzymatic cleavage of its parent molecule, the amyloid beta protein precursor (AbetaPP), there is little information available regarding its in vivo clearance. The E4 isoform of apolipoprotein E (apoE) has been associated with poor clearance of Abeta under in vitro conditions. This is thought to be due to its poor ability to bind Abeta compared with the other common isoforms, apoE2 and apoE3. Although cell culture studies support the notion that Abeta clearance depends upon apoE isoform, validation of these findings requires Abeta clearance studies in vivo. In this study, we examined the clearance of Abeta in vivo from the periphery in mice that expressed apoE (C57BL/6J) or lacked apoE (APOE knockout). We measured the clearance of peripherally injected Abeta over time and additionally, the quantities sequestered by peripheral organs. Western blot analysis of the murine plasma indicated that the half-life of Abeta in the periphery was approximately 15 minutes. The livers of the C57BL/6J mice were found to have sequestered approximately 40% of the total injected Abeta at 90 minutes post-injection, whilst their kidneys contained 5% of the total injected Abeta. In contrast, the livers and kidneys of the APOE knockout animals were found to contain no detectable Abeta. These findings indicate that Abeta is rapidly removed from the plasma by murine peripheral tissues and the rate of its clearance is affected by apoE. |
| Databáze: | OpenAIRE |
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