Biochemical Characterization of Alzheimer's Soluble Amyloid Beta Protein in Human Cerebrospinal Fluid: Association with High Density Lipoproteins

Koudinov, Alexei R.; Koudinova, Natalia V.; Kumar, Asok; Beavis, Ronald C.; Ghiso, Jorge

doi:10.1006/bbrc.1996.0940

Cited by 126 publications

(102 citation statements)

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“…An increase could be explained by deoligomerization of A␤ or the release of A␤ from amyloid-binding proteins, such as (pre)albumin or (apo)lipoproteins. The largest proportion of A␤ in plasma and CSF is bound to proteins (26,27 ). A higher ratio of free to bound A␤ could substantially alter A␤ concentrations.…”

Section: Freezing Delaymentioning

confidence: 99%

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

2015

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BACKGROUND Analyses of cerebrospinal fluid (CSF) biomarkers (β-amyloid protein, total tau protein, and hyperphosphorylated tau protein) are part of the diagnostic criteria of Alzheimer disease. Different preanalytical sample procedures contribute to variability of CSF biomarker concentrations, hampering between-laboratory comparisons. The aim of this study was to explore the influence of fractionated sampling, centrifugation, freezing temperature, freezing delay, and freeze–thaw cycles on CSF biomarker analyses. METHODS We studied fractionated sampling in sequential aliquots of lumbar CSF. Centrifuged and noncentrifuged samples from the same fraction were compared. CSF samples were subjected to different protocols (liquid nitrogen, −80 °C, and −20 °C; 24 h at 2–8 °C; and 24 and 48 h at room temperature). To study the influence of freeze–thaw cycles, samples were thawed up to 4 times and refrozen at −80 °C. CSF was collected in polypropylene tubes. We measured CSF biomarker concentrations with commercially available single-analyte Innotest assays. RESULTS CSF biomarker concentrations from non–blood-contaminated samples are not influenced by centrifugation or fractionated sampling. Freezing temperature and delayed storage can affect biomarker concentrations; freezing of CSF samples at −80 °C as soon as possible after collection is recommended. Consecutive freezing and thawing of CSF samples up to 3 times had little effect. CONCLUSIONS Temperature of freezing, delay until freezing, and freeze–thaw cycles significantly influence CSF biomarker concentrations, stressing the need for standard operating procedures for preanalytical sample handling. The differences observed in this study are, however, relatively small, and the impact on the clinical value of these CSF biomarkers needs to be determined.

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Section: Freezing Delaymentioning

confidence: 99%

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

2015

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“…It is possible that because of isoform-specific interactions between apoE and A/3, there is increased aggregation and deposition or decreased clearance of A/3 in the presence of apoE4 compared with other apoE isoforms. Given these potential interactions, it is noteworthy that soluble A/3 is found associated with lipoproteins in both plasma (Koudinov et a!., 1994;Biere et al, 1996) and CSF (Koudinov et al, 1996). In addition, it is of interest that apoE3 but not apoE4 inhibits A/3-induced neurotoxicity in several in vitro models (Miyata and Smith, 1996;Jordan et al, 1998), suggesting that apoE may have an isoform-specific effect on the toxicity of A~3 in vivo.…”

Section: Figmentioning

confidence: 99%

Nascent Astrocyte Particles Differ from Lipoproteins in CSF

LaDu

Gilligan

Lukens

et al. 1998

Journal of Neurochemistry

259

253

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Abstract:Little is known about lipid transport and metabolism in the brain. As a further step toward understanding the origin and function of CNS lipoproteins, we have characterized by size and density fractionation lipoprotein particles from human CSF and primary cultures of rat astrocytes. The fractions were analyzed for esterified and free cholesterol, triglyceride, phospholipid, albumin, and apolipoproteins (apo) E, Al, All, and J. As determined by lipid and apolipoprotein profiles, gel electrophoresis, and electron microscopy, nascent astrocyte particles contain little core lipid, are primarily discoidal in shape, and contain apoE and apoJ. In contrast, CSF lipoproteins are the size and density of plasma high-density lipoprotein, contain the core lipid, esterified cholesterol, and are spherical. CSF lipoproteins were heterogeneous in apolipoprotein content with apoE, the most abundant apolipoprotein, localized to the largest particles, apoAl and apoAll localized to progressively smaller particles, and apoJ distributed relatively evenly across particle size. There was substantial loss of protein from both CSF and astrocyte particles after density centrifugation compared with gel-filtration chromatography. The differences between lipoproteins secreted by astrocytes and present in CSF suggest that in addition to delivery of their constituents to cells, lipoprotein particles secreted within the brain by astrocytes may have the potential to participate in cholesterol clearance, developing a core of esterified cholesterol before reaching the CSF. Study of the functional properties of both astrocyte-secreted and CSF lipoproteins isolated by techniques that preserve native particle structure may also provide insight into the function of apoE in the pathophysiology of specific neurological diseases such as Alzheimer's disease. Key Words: Apolipoprotein E-Apolipoprotein J -Apolipoprotein Al -Alzheimer's disease-Cholesterol. J. Neurochem. 70, 2070Neurochem. 70, -2081Neurochem. 70, (1998.The intercellular transport of lipids through the aqueous circulatory system requires the packaging of these hydrophobic molecules into water-soluble carriers known as lipoproteins (high-density lipoprotein HDL; low-density lipoprotein LDL; and very-low-density lipoprotein, VLDL). Lipoproteins are macromolecular complexes composed of a phospholipid (PL) and free cholesterol (FC) shell surrounding a triglyceride (TG) and cholesteryl ester (CE) core (see Fig. 6A). Lipoproteins also contain apolipoproteins (apo), proteins that stabilize the surface of lipoproteins as they have both hydrophobic and hydrophilic domains. Apolipoproteins can also serve as cofactors for enzymatic reactions (Fielding et al., 1972) and ligands for cell surface receptors (Brown and Goldstein, 1986). In addition, alterations in apolipoproteins are associated with pathological conditions (Mahley, 1988). Whereas the regulation of lipoprotein metabolism and its effects on systemic lipid regulation have been studied extensively, much less is known about lipid tran...

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“…HSA as a control did not affect the incormodulation of lipid metabolism by AI3 protein and represent poration of [14C]acetate into HepG2 lipids. one of the lipid related functions of sAI3 as an apolipoprotein constituent of HDL [5][6][7]. On the other hand, the high concentrations of A~ peptide (100 and 500 ng m1-1) also studied maximum inhibition, Fig.…”

Section: *T*mentioning

confidence: 99%

“…Experiments were started when cell monoOur studies yielded experimental evidence of sA[~ associalayers became 90% confluent. Cell morphology and ultrastructure tion with high density lipoproteins (HDL) in both normal were monitored by transmissional electron microscopy as previously human plasma [5] and CSF [6,7]. These are the most dense described [15].…”

Section: Introduction In Alzheimer's Brainmentioning

confidence: 99%

Multiple inhibitory effects of Alzheimer's peptide Aβ1–40 on lipid biosynthesis in cultured human HepG2 cells

Koudinova

Березов

Koudinov³

1996

FEBS Letters

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Biochemical Characterization of Alzheimer's Soluble Amyloid Beta Protein in Human Cerebrospinal Fluid: Association with High Density Lipoproteins

Cited by 126 publications

References 0 publications

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

Importance and Impact of Preanalytical Variables on Alzheimer Disease Biomarker Concentrations in Cerebrospinal Fluid

Nascent Astrocyte Particles Differ from Lipoproteins in CSF

Multiple inhibitory effects of Alzheimer's peptide Aβ1–40 on lipid biosynthesis in cultured human HepG2 cells

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