Skip to main content
placeholder image

Defining the function of apolipoprotein-D in Alzheimer's disease

Grant


Scheme


  • Project Grant

Abstract


  • Apolipoprotein-D (apoD) is expressed in the brain and levels are increased in Alzheimerâ¬"s disease (AD) and in amyloidogenic/AD mice (1-3). It is also established that lipid peroxidation is increased in AD and in AD mouse models (4-8). Recent studies revealed an unexpected role for apoD in the control of lipid peroxidation in the brain (9). We propose that apoD may be upregulated in AD inan attempt to combat brain lipid peroxidation. The mechanism underlying the lipid antioxidant function of apoD is a major unsolved puzzle and we have exciting unpublished data indicating that specific apoD Met residues directly reduce lipid-hydroperoxides (L-OOH) thereby inhibiting lipid peroxidation. We hypothesise that early over-expression of apoD in the brain will reduce the AD phenotype in amyloidogenic AD mice whereas apoD gene deletion will exacerbate the phenotype. Using biochemical, cell culture and in vivo approaches, we plan to comprehensively define the function that apoD has in modulating lipid peroxidation and the AD phenotype.

Date/time Interval


  • 2011 - 2013

Sponsor Award Id


  • APP1003886

Local Award Id


  • 11901

Scheme


  • Project Grant

Abstract


  • Apolipoprotein-D (apoD) is expressed in the brain and levels are increased in Alzheimerâ¬"s disease (AD) and in amyloidogenic/AD mice (1-3). It is also established that lipid peroxidation is increased in AD and in AD mouse models (4-8). Recent studies revealed an unexpected role for apoD in the control of lipid peroxidation in the brain (9). We propose that apoD may be upregulated in AD inan attempt to combat brain lipid peroxidation. The mechanism underlying the lipid antioxidant function of apoD is a major unsolved puzzle and we have exciting unpublished data indicating that specific apoD Met residues directly reduce lipid-hydroperoxides (L-OOH) thereby inhibiting lipid peroxidation. We hypothesise that early over-expression of apoD in the brain will reduce the AD phenotype in amyloidogenic AD mice whereas apoD gene deletion will exacerbate the phenotype. Using biochemical, cell culture and in vivo approaches, we plan to comprehensively define the function that apoD has in modulating lipid peroxidation and the AD phenotype.

Date/time Interval


  • 2011 - 2013

Sponsor Award Id


  • APP1003886

Local Award Id


  • 11901