| First Author | Papadopoulos P | Year | 2014 |
| Journal | Neurobiol Aging | Volume | 35 |
| Issue | 1 | Pages | 203-12 |
| PubMed ID | 23954171 | Mgi Jnum | J:211979 |
| Mgi Id | MGI:5577041 | Doi | 10.1016/j.neurobiolaging.2013.07.010 |
| Citation | Papadopoulos P, et al. (2014) Selective benefits of simvastatin in bitransgenic APPSwe,Ind/TGF-beta1 mice. Neurobiol Aging 35(1):203-12 |
| abstractText | Cognitive and cerebrovascular deficits are 2 landmarks of Alzheimer's disease (AD) to target for effective therapy. Here, we evaluated the efficacy of simvastatin in bitransgenic A/T mice overexpressing a mutated form of the human amyloid precursor protein (APP(Swe,Ind)) and a constitutively active form of transforming growth factor-beta1. These mice feature the AD amyloid beta (Abeta) and cerebrovascular pathology. Simvastatin significantly decreased insoluble Abeta peptide levels and Abeta plaque load despite no effect on beta-site amyloid precursor protein-cleaving enzyme and Abeta-degrading enzyme neprilysin protein levels. However, simvastatin failed to improve spatial learning and memory deficits and the decreased baseline levels of the memory-related protein early growth response-1 (Egr-1) in the hippocampus CA1 area. The impaired hyperemic response to whisker stimulation in A/T mice was not improved with treatment, but simvastatin fully restored constitutive nitric oxide synthesis in vessel walls and exacerbated agonist-mediated dilatory deficits. These findings point to the efficacy of simvastatin on selective AD features in a complex model of the disease, likely reflecting the challenges faced by recent clinical trials in assessing statin efficacy. |
