title: Reduced membrane lipids in the cortex of Alzheimer's disease transgenic mice.
abstract: Accumulating evidence suggests that the conversion of Abeta peptides to soluble, neurotoxic polymers is the key event in the development of Alzheimer's disease (AD). Moreover, interactions between Abeta peptides and neuronal membrane lipids likely play a vital role in developing the neurotoxicity associated with AD. The aim of this study is to assess whether lipid matrix of neuronal membranes is affected by the accumulation of Abeta peptides in double transgenic mouse model of AD expressing both mutant human beta-amyloid precursor protein (APP) and presenilin 1 (PS1). We apply high pressure liquid chromatography with an evaporative light scattering detector to compare levels of cholesterol, galactocerebrosides, and phospholipid subclasses simultaneously in cortex samples between AD double transgenic mice at 4 months of age when Abeta production and amyloid plaque deposition is just beginning and at 9 months, when there is advanced Abeta levels and plaque deposition compared to age-matched wild-type (B6/SJL) mice. Both cholesterol (CL) and phospholipids (PL) are significantly lower in 9-month-old AD mice than the same age of B6/SJL mice. Among PL subclasses, phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylcholine (PC) are selectively reduced in 9-month-old AD mice. The molar ratios of CL to PL in 9-month-old AD mice (1.19 +/- 0.27) were significantly higher than those of 9-month-old B6/SJL mice (0.81 +/- 0.08). In keeping with decreased levels of PL, there are also significant reductions of very long-chain n-3 fatty acids (docosahexaenoic acid) and n-6 fatty acid (arachidonic acid) in 9-month-old AD mice. On the other hand, ratios of total n-6 to total n-3 fatty acids were significantly higher in 9-month-old AD mice than in the same age of B6/SJL mice. Taken together, our present data support a role for the interactions of amyloid-beta peptide and neuronal membranes in the subsequent development of AD.
authors: Medical Research Service, VA Pittsburgh Healthcare System, 7180 Highland Drive, Pittsburgh, PA 15206, USA, jkyao@pitt.edu
authors: Jeffrey K
authors: JK
authors: Yao
authors: Thomas M
authors: TM
authors: Wengenack
authors: Geoffry L
authors: GL
authors: Curran
authors: Joseph F
authors: JF
authors: Poduslo
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D005227:Fatty Acids; D008563:Membrane Lipids; D053764:Presenilin-1