@article{9a79ad283cf54ff3a167031fd45ccede,
title = "A novel tau-based rhesus monkey model of Alzheimer's pathogenesis",
abstract = "Introduction: Alzheimer's disease (AD) is a devastating condition with no effective treatments, with promising findings in rodents failing to translate into successful therapies for patients. Methods: Targeting the vulnerable entorhinal cortex (ERC), rhesus monkeys received two injections of an adeno-associated virus expressing a double tau mutation (AAV-P301L/S320F) in the left hemisphere, and control AAV-green fluorescent protein in the right ERC. Noninjected aged-matched monkeys served as additional controls. Results: Within 3 months we observed evidence of misfolded tau propagation, similar to what is hypothesized to occur in humans. Viral delivery of human 4R-tau also coaptates monkey 3R-tau via permissive templating. Tau spreading is accompanied by robust neuroinflammatory response driven by TREM2+ microglia, with biomarkers of inflammation and neuronal loss in the cerebrospinal fluid and plasma. Discussion: These results highlight the initial stages of tau seeding and propagation in a primate model, a more powerful translational approach for the development of new therapies for AD.",
keywords = "Alzheimer's Disease, biomarkers, inflammation, microglia, rhesus monkey, tau",
author = "Danielle Beckman and Paramita Chakrabarty and Sean Ott and Amanda Dao and Eric Zhou and Janssen, {William G.} and Kristine Donis-Cox and Scott Muller and Kordower, {Jeffrey H.} and Morrison, {John H.}",
note = "Funding Information: We want to thank Dr. Benoit I. Giasson for providing the original plasmid expressing the dual tau mutation, Dr. Peter Davies for the tau antibodies, and Dr. Nicholas Kanaan for the tau oligomer antibody. We also thank the UC Davis Alzheimer's Disease Center (P30-AG010129) for providing human CSF and plasma samples and the Bakalar Family. This project was supported by NIH grants P51-OD011107-57S3 and P51-OD011107-58S2. D. Beckman is an Alzheimer's Association Postdoctoral Fellow, AARF-20-685431. The California National Primate Research Center is supported by NIH Office of the Director award P51-OD011107. Funding Information: We want to thank Dr. Benoit I. Giasson for providing the original plasmid expressing the dual tau mutation, Dr. Peter Davies for the tau antibodies, and Dr. Nicholas Kanaan for the tau oligomer antibody. We also thank the UC Davis Alzheimer's Disease Center (P30‐AG010129) for providing human CSF and plasma samples and the Bakalar Family. This project was supported by NIH grants P51‐OD011107‐57S3 and P51‐OD011107‐58S2. D. Beckman is an Alzheimer's Association Postdoctoral Fellow, AARF‐20‐685431. The California National Primate Research Center is supported by NIH Office of the Director award P51‐OD011107. Publisher Copyright: {\textcopyright} 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association",
year = "2021",
month = jun,
doi = "10.1002/alz.12318",
language = "English",
volume = "17",
pages = "933--945",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "John Wiley & Sons Inc.",
number = "6",
}