| Autor: |
Robert Jerome, Sophie Stukas, Button Emily, Cheng Wei-Hang, Lee Michael, Fan Jianjia, Wilkinson Anna, Kulic Iva, Wellington Cheryl L. |
| Rok vydání: |
2015 |
| Zdroj: |
Biochimica et biophysica acta |
| DOI: |
10.1016/j.bbadis.2015.10.005. |
| Popis: |
Many lines of evidence suggest a protective role for high density lipoprotein (HDL) and its major apolipoprotein (apo)A I in Alzheimer's Disease (AD). HDL/apoA I particles are produced by the liver and intestine and in addition to removing excess cholesterol from the body are increasingly recognized to have vasoprotective functions. Here we tested the ability of reconstituted HDL (rHDL) consisting of human apoA I reconstituted with soy phosphatidylcholine for its ability to lower amyloid beta (Aß) levels in symptomatic APP/PS1 mice a well characterized preclinical model of amyloidosis. Animals were treated intravenously either with four weekly doses (chronic study) or a single dose of 60mg/kg of rHDL (acute study). The major finding of our acute study is that soluble brain Aß40 and Aß42 levels were significantly reduced within 24h of a single dose of rHDL. By contrast no changes were observed in our chronic study with respect to soluble or deposited Aß levels in animals assessed 7days after the final weekly dose of rHDL suggesting that beneficial effects diminish as rHDL is cleared from the body. Further rHDL treated animals showed no change in amyloid burden cerebrospinal fluid (CSF) Aß levels neuroinflammation or endothelial activation in the chronic study suggesting that the pathology modifying effects of rHDL may indeed be acute and may be specific to the soluble Aß pool. That systemic administration of rHDL can acutely modify brain Aß levels provides support for further investigation of the therapeutic potential of apoA I based agents for AD. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy Roderick A. Corriveau and Donna M. Wilcock. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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