| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Objectives : SAA, one of the acute phase proteins, is expressed in central nervous system, and increases in the brain of Alzheimer's dementia. This study was aimed to investigate whether SAA dissociates apolipoproteins from cerebrospinal HDL (CSF-HDL) in dose- and time-dependent manners, and if so, whether the dissociated apolipoproteins can be bound to amyloid-β.
Methods : CSF was pooled from neurologically normal subjects. We added PBS or SAA to the pooled CSF. In some experiments, we added amyloid-β to CSF that was mixed with PBS or SAA. The mixture was incubated at 37℃. The distribution of apolipoproteins or amyloid-β in CSF-HDL was analyzed by non-denaturing two-dimensional gel electrophoresis and Western blotting.
Results : SAA but not PBS dissociated apoE, apoAI, and apoAI from CSF-HDL immediately. The SAA concentration required for dissociation of apolipoproteins was the lowest in apoE, the highest in apoAII, and intermediate in apoAI. The more SAA added, the more apolipoproteins dissociated from CSF-HDL. After 2-h incubation, apoE and apoAI further dissociated from CSF-HDL. Amyloid-β was bound to CSF-HDL after 3h-incubation. However, amyloid-β was not bound to the dissociated apolipoproteins.
Conclusions : SAA dissociates apolipoproteins from CSF-HDL in dose- and time-dependent manners. The dissociated apolipoproteins are not bound to amyloid-β. We speculate that chronic mild inflammation in the central nervous system might dissociate apoE form CSF-HDL, and decrease the clearance of amyloid-β from CSF.
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