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Plasma Sphingolipids Predict Alzheimer's Progression

Sensitive blood-based biomarkers indicate disease progression in a dose-dependent manner

FRIDAY, Oct. 7 (HealthDay News) -- Higher plasma levels of ceramides, dihydroceramides (DHCer), sphingomyelins (SM), and dihydrosphingomyelins (DHSM), and ratios of SM/ceramide and DHSM/DHCer are associated with progression in Alzheimer's disease (AD), according to a study published online Aug. 12 in the Journal of Alzheimer's Disease.

Michelle M. Mielke, Ph.D., from the Johns Hopkins University School of Medicine in Baltimore, and colleagues investigated whether plasma levels of ceramides, DHCer, SM, and DHSM, and ratios of SM/ceramide or DHSM/DHCer predicted AD progression. A total of 120 patients with probable AD were followed-up for an average of 4.2 visits and 2.3 years. Electrospray ionization/mass spectrometry was used to assess plasma sphingolipids. The relation between baseline plasma sphingolipid levels and cross-sectional and longitudinal performance on the Mini-Mental State Exam (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating-Sum of Boxes was examined using linear mixed effects models.

The investigators found that there was no cross-sectional association. High levels of DHCer and ceramides correlated with greater AD progression in longitudinal analyses, but the correlation was not significant. High plasma levels of SM, DHSM, and high SM/ceramide, and DHSM/DHCer ratios correlated with less progression on the MMSE and ADAS-Cog, with the ratios providing the strongest prediction for clinical progression. Compared to the lowest tertiles, the highest tertiles of DHSM/DHCer and SM/ceramide ratios increased 3.18 points and 2.42 less per year, respectively, on the ADAS-Cog, and declined 1.35 points and 1.19 less per year, respectively on the MMSE.

"Increased SM/ceramide and DHSM/DHCer ratios dose-dependently predict slower progression among AD patients and may be sensitive blood-based biomarkers for clinical progression," the authors write.

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