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

NEUROBIOLOGY OF AGING

卷:35

Article

Mielke, Michelle M.^1,2  Haughey, Norman J.³  Bandaru, Veera. V. R.³  Zetterberg, Henrik^4,5  Blennowd, Kaj^4,5  Andreasson, Ulf^4,5  Johnson, Sterling C.^6,7,8  Gleason, Carey E.^6,7,8  Blazel, Hanna M.^6,8  Puglielli, Luigi^6,7,8  Sager, Mark A.^6,8,9  Asthana, Sanjay^6,7,8  Carlsson, Cynthia M.^6,7,8 

[1] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA

[3] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA

[4] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden

[5] UCL Inst Neurol, London, England

[6] Univ Wisconsin, Dept Med, Div Geriatr & Gerontol, Sch Med & Publ Hlth, Madison, WI USA

[7] Educ & Clin Ctr GRECC, Madison VA Geriatr Res, Madison, WI USA

[8] Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA

[9] Wisconsin Alzheimers Inst, Madison, WI USA

关键词: Sphingolipids;    Ceramide;    Sphingomyelin;    Cerebrospinal fluid;    Beta-amyloid;    Tau;    Alzheimer's disease;   

DOI  :  10.1016/j.neurobiolaging.2014.05.019

来源: Elsevier

【 摘 要 】

Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (A beta) and tau pathology but in vivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (A beta 1-42, A beta X-38, A beta X-40, and A beta X-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 A beta X-38 (r = 0.312, p = 0.003), AbX-40 (r = 0.327, p = 0.002), and T-tau (r = 0.313, p = 0.003) but not with A beta X-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 Ab 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 Ab and tau levels in cognitively normal individuals at increased risk for Alzheimer's disease, indicating these sphingolipids may be associated with early pathogenesis. (C) 2014 Elsevier Inc. All rights reserved.

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