A nonhuman primate model of early Alzheimer's disease pathologic change: Implications for disease pathogenesis
| Autor: | Thomas C. Register, Angela M. Wilson, Akiva Mintz, Suzanne Craft, Matthew J. Jorgensen, Caitlin S. Latimer, Carol A. Shively, C. Dirk Keene, Joseph A. Maldjian, Rachel N. Andrews, Jay R. Kaplan, Christopher T. Whitlow, Thomas J. Montine, Bryan J. Neth |
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| Rok vydání: | 2018 |
| Předmět: |
Amyloid
Pathology medicine.medical_specialty Epidemiology Neuroimaging Plaque Amyloid Disease Disease pathogenesis Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Cerebrospinal fluid Developmental Neuroscience Alzheimer Disease Nonhuman primate Chlorocebus aethiops Animals Medicine 030304 developmental biology 0303 health sciences Cerebrospinal fluid (CSF) business.industry Health Policy Disease mechanisms Brain Gait speed Disease Models Animal Psychiatry and Mental health Female Neurology (clinical) Tau Geriatrics and Gerontology business Alzheimer’s disease Biomarkers 030217 neurology & neurosurgery Model |
| Zdroj: | Alzheimer's & dementia : the journal of the Alzheimer's Association |
| ISSN: | 1552-5279 1552-5260 |
| DOI: | 10.1016/j.jalz.2018.06.3057 |
| Popis: | Introduction Nonhuman primates may serve as excellent models of sporadic age-associated brain β-amyloid deposition and Alzheimer's disease pathologic changes. We examined whether a vervet nonhuman primate model recapitulated pathologic, physiologic, and behavioral features of early Alzheimer's disease. Methods Nine middle-aged (mean = 11.2 years) and nine aged (mean = 21.7 years) female vervet/African green monkeys underwent cerebrospinal fluid collection, gait speed measurement, and neuroimaging before neuropathologic assessment. Results β-amyloid plaques were identified in all aged vervets and paired helical filament tau immunoreactivity was observed in all animals. Cerebrospinal fluid β-amyloid42 and gait speed correlated negatively with age and plaque density. Greater plaque and paired helical filament tau burden predicted reduced volumes and CMRg in several brain regions. Discussion We observed a coordinated set of relationships among neuropathologic, cerebrospinal fluid, imaging, and behavioral modalities consistent with early Alzheimer's disease. Our results support future use of the vervet model to explore disease mechanisms, biomarkers, and novel therapeutic strategies. |
| Databáze: | OpenAIRE |
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