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From the Laboratory of Neurosciences (Drs. Haughey and Mattson, R.G. Cutler and A. Tammara), National Institute on Aging Gerontology Research Center, Baltimore, MD; and Departments of Neurology (Drs. Haughey, McArthur, Nath, Reid, Vargas, and Pardo), Pathology (Dr. Pardo), and Neuroscience (Dr. Mattson), Johns Hopkins University School of Medicine, Baltimore, MD.
Address correspondence and reprint requests to Dr. Norman J. Haughey, Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6-109, 600 North Wolfe Street, Baltimore, MD 21287; e-mail: nhaughe1{at}jhmi.edu
Background: Polymorphisms in apolipoprotein E have been associated with worse prognoses in numerous neurodegenerative conditions, including HIV dementia (HIVD). Despite these correlative observations, there has been little evidence suggesting a mechanism whereby the expression of ApoE4 renders neurons susceptible to insult.
Methods: Electrospray ionization tandem mass spectrometry was used to quantify levels of sphingolipids and sterols in brains of HIVD patients. Data were stratified according to APOE genotype.
Results: The authors found evidence of dysregulated lipid and sterol metabolism in HIVD patients with an APOE4 genotype. They also found elevations of sphingomyelin, ceramide, and cholesterol in the medial frontal cortex, parietal cortex, and cerebellum of HIVD patients with an APOE3/4 or APOE4/4 genotype compared with HIVD patients with an APOE3/3 genotype. There was no difference in the number of astrocytes or activated microglia in any brain region of the two patient populations, suggesting that modification of lipid metabolism in HIVD patients with an APOE4 genotype was not the result of increased CNS inflammation.
Conclusions: HIV dementia patients with an APOE4 genotype may be sensitized to neural insults because of dysregulations in lipid metabolism.
Received October 28, 2003. Accepted in final form March 28, 2004.
See also page 608
R.G.C. and N.J.H. contributed equally to the work.
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