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.
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, S Mark Taper Imaging Center, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. robert.m.cohen@emory.edu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cohen
authors.forename: Kavon
authors.initials: K
authors.lastname: Rezai-Zadeh
authors.forename: Tara M
authors.initials: TM
authors.lastname: Weitz
authors.forename: Altan
authors.initials: A
authors.lastname: Rentsendorj
authors.forename: David
authors.initials: D
authors.lastname: Gate
authors.forename: Inna
authors.initials: I
authors.lastname: Spivak
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Bholat
authors.forename: Vitaly
authors.initials: V
authors.lastname: Vasilevko
authors.forename: Charles G
authors.initials: CG
authors.lastname: Glabe
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Breunig
authors.forename: Pasko
authors.initials: P
authors.lastname: Rakic
authors.forename: Hayk
authors.initials: H
authors.lastname: Davtyan
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
authors.forename: Serguei
authors.initials: S
authors.lastname: Bannykh
authors.forename: Christine A
authors.initials: CA
authors.lastname: Szekely
authors.forename: Robert N
authors.initials: RN
authors.lastname: Pechnick
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal; D016657:Cerebral Amyloid Angiopathy; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000235:genetics / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016875:tau Proteins