Soluble LR11 competes with amyloid ß in binding to cerebrospinal fluid-high-density lipoprotein.

BACKGROUND: LR11 is a member of the low-density lipoprotein (LDL) receptor family with high expression in neurons. Some cell surface LR11 is cleaved and secreted into the cerebrospinal fluid (CSF) as soluble LR11 (sLR11). Patients with Alzheimer's disease (AD), particularly apolipoprotein E4 carriers, have high CSF-sLR11 and low CSF-amyloid ß (Aß) concentrations. Therefore, we assessed whether sLR11 is bound to CSF-high-density lipoprotein (HDL) and whether sLR11 competes with Aß in binding to apoE in CSF-HDL. METHODS: We measured CSF-sLR11 concentrations (50 controls and 16 patients with AD) using enzyme immunoassay. sLR11 and apoE distribution in the CSF was evaluated using non-denaturing two-dimensional gel electrophoresis (N-2DGE). ApoE bound to sLR11 or Aß was identified using co-immunoprecipitation assay. RESULTS: CSF-sLR11 concentrations were higher in patients with AD than controls (adjusted for sLR11 using phospholipid). N-2DGE analysis showed that sLR11 and Aß comigrated with a large apoE-containing CSF-HDL. Moreover, fewer apoE was bound to Aß when a higher amount of apoE was bound to sLR11 in patients with AD who presented with ε4/4. CONCLUSION: sLR11 binds to CSF-HDL and competes with Aß in binding to apoE in CSF-HDL, indicating that sLR11 affects Aß clearance via CSF-HDL.

Immune-mediated acquired lecithin-cholesterol acyltransferase deficiency: A case report and literature review.

BACKGROUND: Recessive inherited disorder lecithin-cholesterol acyltransferase (LCAT) deficiency causes severe hypocholesterolemia and nephrotic syndrome. Characteristic lipoprotein subfractions have been observed in familial LCAT deficiency (FLD) with renal damage. OBJECTIVE: We described a case of acquired LCAT deficiencies with literature review. METHODS: The lipoprotein profiles examined by gel permeation-high-performance liquid chromatography (GP-HPLC) and native 2-dimensional electrophoresis before and after prednisolone (PSL) treatment. RESULTS: Here we describe the case of a 67-year-old man with severely low levels of cholesterol. The serum LCAT activity was undetectable, and autoantibodies against it were detected. The patient developed nephrotic syndrome at the age of 70 years. Renal biopsy revealed not only membranous glomerulonephritis but also lesions similar to those seen in FLD. We initiated PSL treatment, which resulted in remission of the nephrotic syndrome. In GP-HPLC analysis, lipoprotein profile was similar to that of FLD although lipoprotein X level was low. Acquired LCAT deficiencies are extremely rare with only 7 known cases including ours. Patients with undetectable LCAT activity levels develop nephrotic syndrome that requires PSL treatment; cases whose LCAT activity levels can be determined may also develop nephrotic syndrome, but spontaneously recover. CONCLUSION: Lipoprotein X may play a role in the development of renal impairment in individuals with FLD. However, the effect might be less significant in individuals with acquired LCAT deficiency.

Apolipoproteins C-II and C-III as nutritional markers unaffected by inflammation.

BACKGROUND: Rapid turnover proteins (RTPs), such as transthyretin (TTR), retinol binding protein (RBP), and transferrin (Tf), provide an accurate assessment of nutritional status but are susceptible to inflammation. Lipid-related markers, which have short half-lives in serum, may be better suited for nutritional assessment. We sought to identify sensitive nutritional markers unaffected by inflammation. METHODS: Fasting serum samples were collected from 30 malnourished inpatients and 25 healthy volunteers. Malnourished inpatients were divided into 2 groups: a low-C-reactive protein (CRP) group (CRP < 20 mg/l, n = 15) and a high-CRP group (CRP ≥ 20 mg/l, n = 15). Lipid-related markers, traditional nutritional markers, RTPs, micronutrients, and ketone bodies were measured and compared among the groups. RESULTS: Apolipoprotein (Apo)C-II and ApoC-III concentrations were lower in malnourished inpatients than in the control group. There was no significant difference in ApoC-II and ApoC-III between the low- and high-CRP groups. Carnitine transporters and ketone bodies did not show a significant difference among the three groups. Albumin, TTR, RBP, and Tf concentrations were lowest in the high-CRP group, intermediate in the low-CRP group, and highest in the control group. CONCLUSIONS: These results indicate that ApoC-II and ApoC-III are appropriate nutritional biomarkers unaffected by inflammation.