Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease.
Amyloid-β peptide species accumulating in the brain of patients with Alzheimer's disease are assumed to have a neurotoxic action and hence to be key actors in the physiopathology of this neurodegenerative disease. We have studied a new mouse mutant (APPxPS1-Ki) line developing both early-onset brain amyloid-β deposition and, in contrast to most of transgenic models, subsequent neuronal loss. In 6-month-old mice, we observed cell layer atrophies in the hippocampus, together with a dramatic decrease in neurogenesis and a reduced brain blood perfusion as measured in vivo by magnetic resonance imaging. In these mice, neurological impairments and spatial hippocampal dependent memory deficits were also substantiated and worsened with aging. We described here a phenotype of APPxPS1-Ki mice that summarizes several neuroanatomical alterations and functional deficits evocative of the human pathology. Such a transgenic model that displays strong face validity might be highly beneficial to future research on AD physiopathogeny and therapeutics.
Faure
A
A
CNRS, Lab NAMC, UMR8620, Université Paris Sud, 91405, Orsay, France. alexis.faure@u-psud.fr
Verret
L
L
Bozon
B
B
El Tannir El Tayara
N
N
Ly
M
M
Kober
F
F
Dhenain
M
M
Rampon
C
C
Delatour
B
B
D000367:Age Factors; D000375:Aging; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001007:Anxiety / Q000209:etiology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D009043:Motor Activity / Q000235:genetics; D009069:Movement Disorders / Q000209:etiology; D009154:Mutation / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics*; D009460:Neurologic Examination; D053764:Presenilin-1 / Q000235:genetics*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1