Abstract
Frontotemporal dementia (FTD) is a common cause of early onset dementia with behavioral variant FTD (bvFTD) being the most common form. bvFTD is characterized clinically by behavioral and personality changes, eating abnormalities, and pathologically, by systemic lipid dysregulation that impacts on survival. As lipoprotein metabolism is at the core of lipid dysregulation, here, we analyzed the composition, both proteins and lipids, of the two major lipoprotein classes in blood – high density lipoproteins (HDLs) and low density lipoproteins (LDLs). Fasted plasmas from bvFTD and Alzheimer’s disease (AD) patients and controls were fractionated using fast protein liquid chromatography (FPLC) and samples analyzed by lipid assays, ELISA and western blotting. We found that apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) levels in HDLs were decreased in bvFTD compared to controls, whereas apolipoprotein B (apoB) levels in LDLs were unaltered. We also found that cholesterol and triglyceride levels in FPLC fractions were altered in bvFTD compared to controls. The apoB:apoA-I ratio and the standard lipid ratios were significantly increased in bvFTD compared to AD and controls. Furthermore, we found that plasma apolipoprotein C-I and paraoxonase 1 levels were significantly altered in bvFTD and AD, respectively, compared controls. This study represents the first apolipoprotein analysis of bvFTD, and our results suggest altered HDL function and elevated cardiovascular disease risk in bvFTD.
Highlights
Proper diagnosis and treatment of dementia is a major challenge to public health with the aging of the population
Fasted plasmas from behavioral variant FTD (bvFTD) and Alzheimer’s disease (AD) patients and controls (n = 10, 10, 11) were individually fractionated using fast protein liquid chromatography (FPLC) and 140 samples were collected over a 140-min period; in total 4,340 samples were collected from 31 plasma samples
A typical FPLC chromatogram generated from the inbuilt UV absorption detector revealed three peaks at ∼75, 100 and 115 min that correspond to very low density lipoproteins (VLDLs)/low density lipoproteins (LDLs), high density lipoproteins (HDLs), and human serum albumin (HSA), respectively (Figure 1A)
Summary
Proper diagnosis and treatment of dementia is a major challenge to public health with the aging of the population. Two major causes of dementia are Alzheimer’s disease (AD) and frontotemporal dementia (FTD), with behavioral variant FTD (bvFTD) the most common form of FTD (Piguet et al, 2011). Unlike AD, bvFTD is characterized by considerable early loss of significant amounts of brain tissue with concomitant loss of lipids (Broe et al, 2003; Kril and Halliday, 2004; Kril et al, 2005; Gregory et al, 2006). BvFTD patients are often misdiagnosed as AD because of overlapping clinical traits. A key feature that differentiates bvFTD patients from AD patients is the presence of eating abnormalities
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