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

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

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (Aβ) and tau pathology but invivo 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 36-69years, 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 invivo 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.

Original languageEnglish (US)
Pages (from-to)2486-2494
Number of pages9
JournalNeurobiology of aging
Volume35
Issue number11
DOIs
StatePublished - Nov 1 2014

Keywords

  • Alzheimer's disease
  • Beta-amyloid
  • Ceramide
  • Cerebrospinal fluid
  • Sphingolipids
  • Sphingomyelin
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Fingerprint Dive into the research topics of 'Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease'. Together they form a unique fingerprint.

  • Cite this

    Mielke, M. M., Haughey, N. J., Bandaru, V. V. R., Zetterberg, H., Blennow, K., Andreasson, U., Johnson, S. C., Gleason, C. E., Blazel, H. M., Puglielli, L., Sager, M. A., Asthana, S., & Carlsson, C. M. (2014). Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease. Neurobiology of aging, 35(11), 2486-2494. https://doi.org/10.1016/j.neurobiolaging.2014.05.019