Reduced liver-synthesized lipids may increase Alzheimer’s risk

Reduced levels of plasmalogens synthesized in the liver may adversely affect central nervous system synaptic and antioxidant functions, potentially contributing to cognitive decline in patients with Alzheimer’s disease, according to study results released at the Alzheimer’s Association International Conference 2018.

“The data suggest that reduced production of plasmalogens by the liver may result in reduced availability of these critical lipids to the brain. This may contribute to impaired cognitive function and neurodegeneration in Alzheimer’s,” Mitchel A. Kling, MD, from the Perelman School of Medicine at the University of Pennsylvania, said in the press release. “These data provide a possible explanation for the lack of effect of fish oil or [docosahexaenoic acid (DHA)] on cognitive function or Alzheimer’s in previous studies.”

Kling and colleagues from the Alzheimer’s Disease Metabolics Consortium designed the study to explore plasmalogens and other lipids and their relation to liver-related genes and proteins that may influence brain function via circulating lipoproteins.

The researchers measured four ethanolamine plasmalogens and four closely-related phosphatidylethanolamines in serum from patients enrolled in one of three Alzheimer’s Disease Neuroimaging Initiative (ANDI) studies.

Results showed significant negative associations between baseline Alzheimer’s Disease Assessment Scale-Cognitive 13 (ADAS-Cog13) score with PL-PX ethanolamine plasmalogen remodeling index (coefficient = –0.135; P = 3.24E-6) and ADAS-Cog13 score and overall PBV composite index (coefficient = –0.13; P = 6.92E-5); and between Mini-Mental State Examination with PL-PX (coefficient = 0.04; P = 1.28E-9) and PBV (coefficient = 0.038; P = 6.50E-9).

Lower values of PL-PX (coefficient = –0.244; P = .007) and overall PBV (coefficient = –0.255; P = .005) correlated significantly with an increased risk for Alzheimer’s disease.

“We are now further examining the connections between plasmalogens and other lipids vs. cognition, associations with gene expression in liver and brain, and network modeling approaches,” Kling wrote in conclusion. – by Talitha Bennett

Reference:

Kling MA, et al. Serum indices of ethanolamine plasmalogens and phosphatide metabolism in the combined ADNI-1/GO/2 cohort: Does the liver contribute to AD risk by failing to supply key lipids to the brain? Presented at: Alzheimer's Association International Conference; July 22-26, 2018; Chicago.

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