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Isolation of High-density Lipoproteins for Non-coding Small RNA Quantification
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Altered High Density Lipoprotein Composition in Behavioral Variant Frontotemporal Dementia.

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Frontiers in Neuroscience
|November 30, 2018
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Behavioral variant frontotemporal dementia (bvFTD) is linked to altered lipid profiles. This study found changes in high-density lipoprotein (HDL) function, suggesting increased cardiovascular disease risk in bvFTD patients.

Keywords:
Alzheimer’s diseaseHDLLDLapolipoproteinbiomarkercardiovascular disease riskfrontotemporal dementialipid

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Cardiovascular Science

Background:

  • Frontotemporal dementia (FTD), particularly the behavioral variant (bvFTD), is a leading cause of early-onset dementia.
  • bvFTD presents with behavioral changes and is pathologically associated with systemic lipid dysregulation impacting survival.
  • Lipoprotein metabolism is central to lipid dysregulation, making its analysis crucial for understanding bvFTD.

Purpose of the Study:

  • To analyze the protein and lipid composition of high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) in patients with bvFTD.
  • To investigate alterations in lipoprotein metabolism and their potential link to disease progression and cardiovascular risk in bvFTD.
  • To compare lipid profiles between bvFTD patients, Alzheimer's disease (AD) patients, and healthy controls.

Main Methods:

  • Fasted plasma samples from bvFTD patients, AD patients, and controls were fractionated using fast protein liquid chromatography (FPLC).
  • Lipid assays, ELISA, and western blotting were employed to analyze the composition of lipoprotein fractions.
  • Key proteins such as apolipoproteins (apoA-I, apoA-II, apoB, apoC-I) and lipids (cholesterol, triglycerides) were quantified.

Main Results:

  • HDL-associated apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) levels were decreased in bvFTD patients compared to controls.
  • Low-density lipoprotein (LDL) apolipoprotein B (apoB) levels remained unaltered in bvFTD.
  • Cholesterol and triglyceride levels were altered in FPLC fractions of bvFTD patients. The apoB:apoA-I ratio and standard lipid ratios were significantly elevated in bvFTD compared to AD and controls. Plasma apolipoprotein C-I and paraoxonase 1 levels were altered in bvFTD and AD, respectively.

Conclusions:

  • This study provides the first apolipoprotein analysis in bvFTD, revealing significant alterations in HDL composition and function.
  • The findings suggest an elevated risk of cardiovascular disease in individuals with bvFTD.
  • Further research into lipoprotein dysregulation in bvFTD may offer new therapeutic targets and diagnostic markers.