Oral apolipoprotein A-I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer's disease

Autor: Shaila P. Handattu, David W. Garber, Candyce E. Monroe, Thomas van Groen, Inga Kadish, Gaurav Nayyar, Dongfeng Cao, Mayakonda N. Palgunachari, Ling Li, G.M. Anantharamaiah
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: Neurobiology of Disease, Vol 34, Iss 3, Pp 525-534 (2009)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2009.03.007
Popis: Recent evidence indicates that inflammation may significantly contribute to the pathogenesis of Alzheimer's disease (AD). Since the apo A-I mimetic peptide D-4F has been shown to inhibit atherosclerotic lesion formation and regress already existing lesions (in the presence of pravastatin) and the peptide also decreases brain arteriole inflammation, we undertook a study to evaluate the efficacy of oral D-4F co-administered with pravastatin on cognitive function and amyloid β (Aβ) burden in the hippocampus of APPSwe-PS1ΔE9 mice. Three groups of male mice were administered D-4F and pravastatin, Scrambled D-4F (ScD-4F, a control peptide) and pravastatin in drinking water, while drinking water alone served as control. The escape latency in the Morris Water Maze test was significantly shorter for the D-4F+statin administered animals compared to the other two groups. While the hippocampal region of the brain was covered with 4.2±0.5 and 3.8±0.6% of Aβ load in the control and ScD-4F+statin administered groups, in the D-4F+statin administered group Aβ load was only 1.6±0.1%. Furthermore, there was a significant decrease in the number of activated microglia (p
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