Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice
| Autor: | Andrew M. Jenner, Maria D. Ganfornina, Sonia Sanz Muñoz, Diego Sanchez, Hua Zhao, Kalani Ruberu, Tim Karl, Hongyun Li, Brett Garner, Adena S. Spiro, Eric Rassart |
|---|---|
| Přispěvatelé: | National Health and Medical Research Council (Australia) |
| Rok vydání: | 2015 |
| Předmět: |
Genetically modified mouse
Aging Pathology medicine.medical_specialty Apolipoprotein D Neuregulin-1 BACE1-AS Mice Transgenic Plaque Amyloid Hippocampal formation Hippocampus Amyloid beta-Protein Precursor Alzheimer Disease Internal medicine mental disorders medicine Amyloid precursor protein Animals Aspartic Acid Endopeptidases Neurodegeneration Apolipoproteins D Amyloid pathology biology Chemistry General Neuroscience P3 peptide Amyloid β Alzheimer's disease medicine.disease Biochemistry of Alzheimer's disease Disease Models Animal Endocrinology Proteolysis biology.protein Neurology (clinical) Amyloid Precursor Protein Secretases Geriatrics and Gerontology Developmental Biology |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2015.02.010 |
| Popis: | et al. Apolipoprotein D (apoD) is expressed in the brain and levels are increased in affected brain regions in Alzheimer's disease (AD). The role that apoD may play in regulating AD pathology has not been addressed. Here, we crossed both apoD-null mice and Thy-1 human apoD transgenic mice with APP-PS1 amyloidogenic AD mice. Loss of apoD resulted in a nearly 2-fold increase in hippocampal amyloid plaque load, as assessed by immunohistochemical staining. Conversely, transgenic expression of neuronal apoD reduced hippocampal plaque load by approximately 35%. This latter finding was associated with a 60% decrease in amyloid β 1-40 peptide levels, and a 34% decrease in insoluble amyloid β 1-42 peptide. Assessment of β-site amyloid precursor protein cleaving enzyme-1 (BACE1) levels and proteolytic products of amyloid precursor protein and neuregulin-1 point toward a possible association of altered BACE1 activity in association with altered apoD levels. In conclusion, the current studies provide clear evidence that apoD regulates amyloid plaque pathology in a mouse model of AD. This research was supported by the National Health and Medical Research Council (NHMRC) of Australia (Grant ID #1065982) awarded to TK and BG. TK and BG are supported by an NHMRC Research Fellowships (Grant ID #1045643 and #630445, respectively). |
| Databáze: | OpenAIRE |
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