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

Michelle M. Mielke, Norman 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

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

Fingerprint

Sphingolipids
Sphingomyelins
Ceramides
Amyloid
Cerebrospinal Fluid
Alzheimer Disease
Carbon
Genotype
Pathology

Keywords

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

ASJC Scopus subject areas

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

Cite this

Mielke, M. M., Haughey, N., Bandaru, V. V. R., Zetterberg, H., Blennow, K., Andreasson, U., ... 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

Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease. / Mielke, Michelle M.; Haughey, Norman; Bandaru, Veera V R; Zetterberg, Henrik; Blennow, Kaj; Andreasson, Ulf; Johnson, Sterling C.; Gleason, Carey E.; Blazel, Hanna M.; Puglielli, Luigi; Sager, Mark A.; Asthana, Sanjay; Carlsson, Cynthia M.

In: Neurobiology of Aging, Vol. 35, No. 11, 01.11.2014, p. 2486-2494.

Research output: Contribution to journalArticle

Mielke, MM, Haughey, N, Bandaru, VVR, Zetterberg, H, Blennow, K, Andreasson, U, Johnson, SC, Gleason, CE, Blazel, HM, Puglielli, L, Sager, MA, Asthana, S & Carlsson, CM 2014, 'Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease', Neurobiology of Aging, vol. 35, no. 11, pp. 2486-2494. https://doi.org/10.1016/j.neurobiolaging.2014.05.019
Mielke, Michelle M. ; Haughey, Norman ; Bandaru, Veera V R ; Zetterberg, Henrik ; Blennow, Kaj ; Andreasson, Ulf ; Johnson, Sterling C. ; Gleason, Carey E. ; Blazel, Hanna M. ; Puglielli, Luigi ; Sager, Mark A. ; Asthana, Sanjay ; Carlsson, Cynthia M. / Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease. In: Neurobiology of Aging. 2014 ; Vol. 35, No. 11. pp. 2486-2494.
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