Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:32

Article

Faure, A.¹  Verret, L.^2,3  Bozon, B.¹  El Tayara, N. El Tannir^4,5  Ly, M.¹  Kober, F.⁶  Dhenain, M.^7,8,9  Rampon, C.^2,3  Delatour, B.¹ 

[1] Univ Paris 11, UMR8620, Lab NAMC, CNRS, F-91405 Orsay, France

[2] Univ Toulouse, UPS, Ctr Rech Cognit Anim, F-31062 Toulouse 9, France

[3] CNRS, Ctr Rech Cognit Anim, F-31062 Toulouse, France

[4] Ctr Univ Orsay, Lab 112, INSERM, U759, F-91405 Orsay, France

[5] Ctr Univ Orsay, Lab 112, Inst Curie, F-91405 Orsay, France

[6] Univ Mediterranee, Fac Med, UMR CNRS 6612, CRMBM, Marseille, France

[7] CEA, DSV, I2BM, SHFJ,MIRCen Program, F-91401 Orsay, France

[8] CNRS, URA 2210, F-91401 Orsay, France

[9] CEA, DSV, I2BM, Ctr CEA Saclay, F-91191 Gif Sur Yvette, France

关键词: Alzheimer's disease;    Amyloid-beta peptide;    Hippocampus;    Neurogenesis;    Learning and memory;    Brain blood perfusion;   

DOI  :  10.1016/j.neurobiolaging.2009.03.009

来源: Elsevier

【 摘 要 】

Amyloid-beta 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-beta 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 dependant 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. (C) 2009 Elsevier Inc. All rights reserved.

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