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A nonhuman primate model of early Alzheimer's disease pathologic change: Implications for disease pathogenesis
Author(s) -
Latimer Caitlin S.,
Shively Carol A.,
Keene C. Dirk,
Jorgensen Matthew J.,
Andrews Rachel N.,
Register Thomas C.,
Montine Thomas J.,
Wilson Angela M.,
Neth Bryan J.,
Mintz Akiva,
Maldjian Joseph A.,
Whitlow Christopher T.,
Kaplan Jay R.,
Craft Suzanne
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.3057
Subject(s) - cerebrospinal fluid , disease , pathology , neuroimaging , pathogenesis , alzheimer's disease , medicine , degenerative disease , amyloid (mycology) , neuroscience , psychology
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‐amyloid 42 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.