ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain

Bandaru, Veera Venkata Ratnam; Troncoso, Juan; Wheeler, David; Pletnikova, Olga; Wang, Jessica; Conant, Kathy; Haughey, Norman J.

doi:10.1016/j.neurobiolaging.2007.07.024

« Previous Next »Neurobiology of Aging
Volume 30, Issue 4 , Pages 591-599, April 2009

ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain

Veera Venkata Ratnam Bandaru
- Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States
Juan Troncoso
- Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States
- Department of Pathology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States
David Wheeler
- Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States
Olga Pletnikova
- Department of Pathology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States
Jessica Wang
- Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States
Kathy Conant
- Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States
Norman J. Haughey
- Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States
- Corresponding author. Tel.: +1 443 287 3825; fax: +1 410 955 0672.

Received 20 April 2007; received in revised form 17 July 2007; accepted 25 July 2007. published online 21 September 2007.

Abstract

The ɛ4 allele of ApoE is associated with an earlier onset and faster progression of Alzheimer's disease in patients with the familial form of this neurodegenerative condition. Although ApoE4 has been repeatedly associated with altered sphingomyelin and cholesterol levels in tissue culture and rodent models, there has not been a direct quantification of sphingomyelin or sterol levels in the brains of patients with different forms of ApoE. We measured the sphingolipid and sterol content of human brain tissues and found no evidence of perturbed sterol or sphingolipid biochemistry in the brains of individuals expressing ApoE4 who did not have a preexisting neurodegenerative condition. Nevertheless, ApoE4 was associated with gross abnormalities in the sterol and sphingolipid content of numerous brain regions in patients with Alzheimer's diseaase. The findings suggest that ApoE4 may not by itself alter sterol or sphingolipid metabolism in the brain under normal conditions, but that other neuropathologic changes of Alzheimer's are required to unmask the effect of ApoE4, and to perturb sterol and sphingolipid biochemistry.

Keywords: Alzheimer's disease, Apolipoprotein, ApoE, ApoE4, Sterol, Cholesterol, Sphingomeylin, Ceramide, Sphingolipid