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

doi:10.1523/JNEUROSCI.3672-12.2013

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

Neurology

Research output: Contribution to journal › Article › peer-review

360 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 (APP_sw) 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 language	English (US)
Pages (from-to)	6245-6256
Number of pages	12
Journal	Journal of Neuroscience
Volume	33
Issue number	15
DOIs	https://doi.org/10.1523/JNEUROSCI.3672-12.2013
State	Published - Apr 10 2013

ASJC Scopus subject areas

General Neuroscience

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10.1523/JNEUROSCI.3672-12.2013

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Cohen, R. M., Rezai-Zadeh, K., Weitz, T. M., Rentsendorj, A., Gate, D., Spivak, I., Bholat, Y., Vasilevko, V., Glabe, C. G., Breunig, J. J., Rakic, P., Davtyan, H., Agadjanyan, M. G., Kepe, V., Barrio, J. R., Bannykh, S., Szekely, C. A., Pechnick, R. N., & Town, T. (2013). A transgenic alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric Aβ, and frank neuronal loss. Journal of Neuroscience, 33(15), 6245-6256. https://doi.org/10.1523/JNEUROSCI.3672-12.2013

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

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.",

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

year = "2013",

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day = "10",

doi = "10.1523/JNEUROSCI.3672-12.2013",

language = "English (US)",

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Cohen, RM, Rezai-Zadeh, K, Weitz, TM, Rentsendorj, A, Gate, D, Spivak, I, Bholat, Y, Vasilevko, V, Glabe, CG, Breunig, JJ, Rakic, P, Davtyan, H, Agadjanyan, MG, Kepe, V, Barrio, JR, Bannykh, S, Szekely, CA, Pechnick, RN & Town, T 2013, 'A transgenic alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric Aβ, and frank neuronal loss', Journal of Neuroscience, vol. 33, no. 15, pp. 6245-6256. https://doi.org/10.1523/JNEUROSCI.3672-12.2013

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T1 - A transgenic alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric Aβ, and frank neuronal loss

AU - Cohen, Robert M.

AU - Rezai-Zadeh, Kavon

AU - Weitz, Tara M.

AU - Rentsendorj, Altan

AU - Gate, David

AU - Spivak, Inna

AU - Bholat, Yasmin

AU - Vasilevko, Vitaly

AU - Glabe, Charles G.

AU - Breunig, Joshua J.

AU - Rakic, Pasko

AU - Davtyan, Hayk

AU - Agadjanyan, Michael G.

AU - Kepe, Vladimir

AU - Barrio, Jorge R.

AU - Bannykh, Serguei

AU - Szekely, Christine A.

AU - Pechnick, Robert N.

AU - Town, Terrence

PY - 2013/4/10

Y1 - 2013/4/10

N2 - 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.

AB - 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.

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ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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