Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease.
The APP/PS1ki mouse model for Alzheimer's disease (AD) exhibits robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss starting at 6 months of age. It expresses human mutant APP751 with the Swedish and London mutations together with two FAD-linked knocked-in mutations (PS1 M233T and PS1 L235P) in the murine PS1 gene. The present report covers a phenotypical analysis of this model using either behavioral tests for working memory and motor performance, as well as an analysis of weight development and body shape. At the age of 6 months, a dramatic, age-dependent change in all of these properties and characteristics was observed, accompanied by a significantly reduced ability to perform working memory and motor tasks. The APP/PS1ki mice were smaller and showed development of a thoracolumbar kyphosis, together with an incremental loss of body weight. While 2-month-old APP/PS1ki mice were inconspicuous in all of these tasks and properties, there is a massive age-related impairment in all tested behavioral paradigms. We have previously reported robust axonal degeneration in brain and spinal cord, as well as abundant hippocampal CA1 neuron loss starting at 6 months of age in the APP/PS1ki mouse model, which coincides with the onset of motor and memory deficits described in the present report.
Wirths
Oliver
O
Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, D-37075 Goettingen, Germany. owirths@uni-goettingen.de
Breyhan
Henning
H
Schäfer
Stephanie
S
Roth
Christian
C
Bayer
Thomas A
TA
D000544:Alzheimer Disease / Q000150:complications / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008568:Memory; D008569:Memory Disorders / Q000150:complications / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D011597:Psychomotor Performance
D016564:Amyloid beta-Protein Precursor