Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease.

Abstract

Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (Aβ) and tau pathology but in vivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (Aβ1-42, AβX-38, AβX-40, and AβX-42) and tau (T-tau and p-tau181) in 91 cognitively normal individuals, aged 36-69 years, with a parental history of Alzheimer's disease. The 18-carbon acyl chain length ceramide species was associated with AβX-38 (r = 0.312, p = 0.003), AβX-40 (r = 0.327, p = 0.002), and T-tau (r = 0.313, p = 0.003) but not with AβX-42 (r = 0.171, p = 0.106) or p-tau (r = 0.086, p = 0.418). All sphingomyelin species correlated (most p < 0.001) with all Aβ species and T-tau; many also correlated with p-tau. Results remained in regression models after controlling for age and APOE genotype. These results suggest in vivo relationships between cerebrospinal fluid ceramides and sphingomyelins and Aβ and tau levels in cognitively normal individuals at increased risk for Alzheimer's disease, indicating these sphingolipids may be associated with early pathogenesis.

• Authors: Michelle M Mielke, Norman J Haughey, Veera V R Bandaru, Henrik Zetterberg, Kaj Blennow, Ulf Andreasson, Sterling C Johnson, Carey E Gleason, Hanna M Blazel, Luigi Puglielli, Mark A Sager, Sanjay Asthana, Cynthia M Carlsson
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 35 Issue 11 Pg. 2486-2494 (Nov 2014) ISSN: 1558-1497 [Electronic] United States
• PMID: 24952994 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Apolipoproteins E
• Ceramides
• Sphingomyelins
• tau Proteins

Topics

• Adult
• Aged
• Alzheimer Disease (cerebrospinal fluid, etiology, genetics, psychology)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Apolipoproteins E (genetics)
• Ceramides (cerebrospinal fluid)
• Cognition
• Female
• Genotype
• Humans
• Male
• Middle Aged
• Risk
• Sphingomyelins (cerebrospinal fluid)
• tau Proteins (cerebrospinal fluid)