Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer's disease.
Recently, interest in the rat as an animal model of Alzheimer's disease (AD) has been growing. We have previously described the Tg6590 transgenic rat line expressing the amyloid precursor protein containing the Swedish AD mutation (K670M/N671L) that shows early stages of Abeta deposition, predominantly in cerebrovascular blood vessels, after 15 months of age. Here we show that by the age of 9 months, that is long before the appearance of Abeta deposits, the Tg6590 rats exhibit deficits in the Morris water maze spatial navigation task and altered spontaneous behaviour in the open-field test. The levels of soluble Abeta were elevated both in the hippocampus and cortex of transgenic animals. Magnetic resonance imaging showed no major changes in the brains of transgenic animals, although they tended to have enlarged lateral ventricles when compared to control animals. The Tg6590 transgenic rat line should prove a suitable model of early AD for advanced studies including serial cerebrospinal fluid sampling, electrophysiology, neuroimaging or complex behavioural testing.
Kloskowska
Ewa
E
Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden.
Pham
Therese M
TM
Nilsson
Tatjana
T
Zhu
Shunwei
S
Oberg
Johanna
J
Codita
Alina
A
Pedersen
Lars A
LA
Pedersen
Jan T
JT
Malkiewicz
Katarzyna
K
Winblad
Bengt
B
Folkesson
Ronnie
R
Benedikz
Eirikur
E
D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D055647:Rats, Transgenic; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D016875:tau Proteins