Aβ aggregation profiles and shifts in APP processing favor amyloidogenesis in canines
| Autor: | Viorela Pop, M. Paul Murphy, Carl W. Cotman, Elizabeth Head, Christa M. Studzinski, Adam M. Weidner, Nicole C. Berchtold, Charles G. Glabe |
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| Rok vydání: | 2012 |
| Předmět: |
Aging
ADAM10 Plaque Amyloid Article Amyloid beta-Protein Precursor Dogs Alzheimer Disease medicine Insulin-degrading enzyme Animals Humans Cognitive decline Temporal cortex Amyloid beta-Peptides biology Chemistry General Neuroscience P3 peptide Human brain medicine.disease Temporal Lobe Cell biology Disease Models Animal medicine.anatomical_structure Biochemistry biology.protein Neurology (clinical) Amyloid Precursor Protein Secretases Geriatrics and Gerontology Alzheimer's disease Amyloid precursor protein secretase Developmental Biology |
| Zdroj: | Neurobiology of Aging. 33:108-120 |
| ISSN: | 0197-4580 |
| Popis: | The aged canine is a higher animal model that naturally accumulates β-amyloid (Aβ) and shows age-related cognitive decline. However, profiles of Aβ accumulation in different species (40 vs. 42), its assembly states, and Aβ precursor protein (APP) processing as a function of age remain unexplored. In this study, we show that Aβ increases progressively with age as detected in extracellular plaques and biochemically extractable Aβ40 and Aβ42 species. Soluble oligomeric forms of the peptide, with specific increases in an Aβ oligomer migrating at 56kDa, also increase with age. Changes in APP processing could potentially explain why Aβ accumulates, and we show age-related shifts towards decreased total APP protein and non-amyloidogenic (α-secretase) processing coupled with increased amyloidogenic (β-secretase) cleavage of APP. Importantly, we describe Aβ pathology in the cingulate and temporal cortex and provide a description of oligomeric Aβ across the canine lifespan. Our findings are in line with observations in the human brain, suggesting that canines are a valuable higher animal model for the study of Aβ pathogenesis. |
| Databáze: | OpenAIRE |
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