A transgenic alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric Aβ, and frank neuronal loss

Robert M. Cohen, Kavon Rezai-Zadeh, Tara M. Weitz, Altan Rentsendorj, David Gate, Inna Spivak, Yasmin Bholat, Vitaly Vasilevko, Charles G. Glabe, Joshua J. Breunig, Pasko Rakic, Hayk Davtyan, Michael G. Agadjanyan, Vladimir Kepe, Jorge R. Barrio, Serguei Bannykh, Christine A. Szekely, Robert N. Pechnick, Terrence Town*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

234 Scopus citations

Abstract

Alzheimer's disease (AD) is hallmarked by amyloid plaques, neurofibrillary tangles, and widespread cortical neuronal loss (Selkoe, 2001). The "amyloid cascade hypothesis" posits that cerebral amyloid sets neurotoxic events into motion that precipitate Alzheimer dementia (Hardy and Allsop, 1991). Yet, faithful recapitulation of all AD features in widely used transgenic (Tg) mice engineered to overproduce Aβ peptides has been elusive. We have developed a Tg rat model (line TgF344-AD) expressing mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1ΔE9) genes, each independent causes of early-onset familial AD. TgF344-AD rats manifest age-dependent cerebral amyloidosis that precedes tauopathy, gliosis, apoptotic loss of neurons in the cerebral cortex and hippocampus, and cognitive disturbance. These results demonstrate progressive neurodegeneration of the Alzheimer type in these animals. The TgF344-AD rat fills a critical need for a next-generation animal model to enable basic and translational AD research.

Original languageEnglish (US)
Pages (from-to)6245-6256
Number of pages12
JournalJournal of Neuroscience
Volume33
Issue number15
DOIs
StatePublished - Apr 10 2013
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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