Normal cognition in transgenic BRI2-Aβ mice

Molecular Neurodegeneration

Christopher Janus²  Todd Golde²  David R Borchelt²  Dennis W Dickson¹  Amelia March²  Amanda Hanna¹  Paramita Chakrabarty²  Jungsu Kim³ 

[1] Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA;Department of Neuroscience and Center for Translational Research in Neurodegenerative Disease, University of Florida, 1275 Center Dr., Box 100159, Gainesville, FL 32610, USA;Current address: Department of Neurology, Washington University School of Medicine, 660 S. Euclid Box 811, St. Louis, MO 63110, USA

关键词: Cognition;    Amyloid plaques;    Amyloid-β;    Mouse models;    Alzheimer’s disease;   

Others  :  863266
DOI  :  10.1186/1750-1326-8-15

 received in 2013-02-11, accepted in 2013-05-08,  发布年份 2013

【 摘 要 】

Background

Recent research in Alzheimer’s disease (AD) field has been focused on the potential role of the amyloid-β protein that is derived from the transmembrane amyloid precursor protein (APP) in directly mediating cognitive impairment in AD. Transgenic mouse models overexpressing APP develop robust AD-like amyloid pathology in the brain and show various levels of cognitive decline. In the present study, we examined the cognition of the BRI2-Aβ transgenic mouse model in which secreted extracellular Aβ1-40, Aβ1-42 or both Aβ1-40/Aβ1-42 peptides are generated from the BRI-Aβ fusion proteins encoded by the transgenes. BRI2-Aβ mice produce high levels of Aβ peptides and BRI2-Aβ1-42 mice develop amyloid pathology that is similar to the pathology observed in mutant human APP transgenic models.

Results

Using established behavioral tests that reveal deficits in APP transgenic models, BRI2-Aβ1-42 mice showed completely intact cognitive performance at ages both pre and post amyloid plaque formation. BRI2-Aβ mice producing Aβ1-40 or both peptides were also cognitively intact.

Conclusions

These data indicate that high levels of Aβ1-40 or Aβ1-42, or both produced in the absence of APP overexpression do not reproduce memory deficits observed in APP transgenic mouse models. This outcome is supportive of recent data suggesting that APP processing derivatives or the overexpression of full length APP may contribute to cognitive decline in APP transgenic mouse models. Alternatively, Aβ aggregates may impact cognition by a mechanism that is not fully recapitulated in these BRI2-Aβ mouse models.

【 授权许可】

   
2013 Kim et al.; licensee BioMed Central Ltd.

【 图 表 】

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