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Neurobiol Aging. 2014 Nov;35(11):2486-94. doi: 10.1016/j.neurobiolaging.2014.05.019. Epub 2014 May 27.

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

Author information

1
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address: mielke.michelle@mayo.edu.
2
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
3
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, London, UK.
4
Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Madison VA Geriatric Research, Education and Clinical Center (GRECC), Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA.
5
Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA.
6
Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA; Wisconsin Alzheimer's Institute, Madison, WI, USA.

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.

KEYWORDS:

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

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