Mielke Michelle M, Haughey Norman J, 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
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Neurobiol Aging. 2014 Nov;35(11):2486-2494. doi: 10.1016/j.neurobiolaging.2014.05.019. Epub 2014 May 27.
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.
细胞研究表明，鞘脂可能导致或加速β-淀粉样蛋白（Aβ）和tau蛋白病变，但缺乏体内人体研究。我们测定了91名36至69岁认知正常、有阿尔茨海默病家族史个体的脑脊液中鞘脂（神经酰胺和鞘磷脂）、β-淀粉样蛋白（Aβ1-42、AβX-38、AβX-40和AβX-42）以及tau蛋白（总tau蛋白和磷酸化tau蛋白181）的水平。18碳酰基链长度的神经酰胺种类与AβX-38（r = 0.312，p = 0.003）、AβX-40（r = 0.327，p = 0.002）和总tau蛋白（r = 0.313，p = 0.003）相关，但与AβX-42（r = 0.171，p = 0.106）或磷酸化tau蛋白（r = 0.086，p = 0.418）无关。所有鞘磷脂种类均与所有Aβ种类和总tau蛋白相关（大多数p < 0.001）；许多还与磷酸化tau蛋白相关。在控制年龄和APOE基因型后，结果在回归模型中仍然成立。这些结果表明，在患阿尔茨海默病风险增加的认知正常个体中，脑脊液神经酰胺和鞘磷脂与Aβ和tau蛋白水平之间存在体内相关性，表明这些鞘脂可能与早期发病机制有关。
