Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry

Han, Xianlin; Holtzman, David M.; McKeel, Daniel W.

doi:10.1046/j.1471-4159.2001.00332.x

Cited by 510 publications

(479 citation statements)

References 65 publications

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“…Although the phosphatidyl subclass of phospholipids is predominant in most cellular membrane lipids, plasmenyl subclass species are the major phospholipid component in neuronal cell membranes (22,23). Lipid molecular species containing very long fatty acyl chains (e.g., 22 and 24 carbons) are enriched in the nervous system relative to the other organs.…”

Section: The Nervous System Contains the Largest Diversity Of Lipid Cmentioning

confidence: 99%

“…By using multi-dimensional MS-based shotgun lipidomics, we have identified distinct lipid profiles of GPEtn in gray matter and white matter in human brain (23). Briefly, negative-ion ESI/MS analyses of chloroform extracts of cortex gray matter from cognitively normal, postmortem subjects in the presence of a small amount of LiOH demonstrate multiple predominant deprotonated ion peaks corresponding to GPEtn molecular species ( Figure 5A).…”

Section: Neurolipidomics Reveals Distinct Lipid Profiles Of Ethanolammentioning

confidence: 99%

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Neurolipidomics: challenges and developments

Han

2007

Front Biosci

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101

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The field of lipidomics is one of the most rapidly expanding areas of systems biology research. Considering the uniqueness and complexity of the lipidome in the nervous system (i.e., neurolipidome), neurolipidomics remains quite challenging but exciting. With the recent development of mass spectrometry (MS)-based lipidomics, particularly the rapid improvement of multi-dimensional MS-based shotgun lipidomics, much progress has been made in neurolipidomics. As the accelerated development of future technologies enables lipidomics penetrance into lower and lower abundance regions of mass contents of individual lipid molecular species, it can be anticipated that many biochemical mechanisms underlying lipid metabolism critical to neuronal disease states will be increasingly uncovered. Through exploiting the information content inherent in the complexity of neuronal lipid composition and kinetic turnover which can be revealed by neurolipidomics, substantial insights into neuronal plasticity and gene function can be gathered. Through neurolipidomics, the markers for these neuronal diseases which identify pathological alterations and are diagnostic of disease onset, progression or severity may potentially be discovered. Accordingly, with neurolipidomics, our understanding of the complexities of the nervous system will be undoubtedly accelerated, as many mysteries are resolved.

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Section: The Nervous System Contains the Largest Diversity Of Lipid Cmentioning

confidence: 99%

Section: Neurolipidomics Reveals Distinct Lipid Profiles Of Ethanolammentioning

confidence: 99%

Neurolipidomics: challenges and developments

Han

2007

Front Biosci

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101

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“…Cultures were then incubated in 5 ml of serum-free Dulbecco's modified Eagle's medium/Ham's F-12 (1:1) medium containing N2 supplement (Invitrogen) for an additional 72 h. Conditioned media were collected and apoE3 or apoE4 lipoproteins were purified from the corresponding conditioned media with the anti-apoE immunoaffinity column. , and N17:0 Cer (5 nmol/mg of protein) (used as internal standards for the quantification of choline-containing phospholipids, ethanolamine-containing phospholipids, anionic lipids (including PtdGro, phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer), and ST), GalC, and Cer, respectively) and similarly prepared as described previously (20,30,31). Lipids were similarly extracted from human CSF and astrocyte-secreted lipoproteins in the presence of N16:0 ST (270 pmol/mg of CSF protein and 2 nmol/mg apoE, respectively) (used as internal standard for the quantification of ST).…”

Section: Materials-syntheticmentioning

confidence: 99%

“…ESI/MS analyses of lipids were performed utilizing a Finnigan TSQ-7000 spectrometer equipped with an electrospray ion source as described (20,30,32). All molecular species were directly quantitated by comparisons of the individual ion peak intensities with a properly selected internal standard (e.g.…”

Section: Preparation and Quantitation Of Lipids From Mouse Brain Tissmentioning

confidence: 99%

Novel Role for Apolipoprotein E in the Central Nervous System

Han

Cheng

Fryer

et al. 2003

Journal of Biological Chemistry

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122

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It has long been postulated that apolipoprotein E (apoE) may play a role in lipid metabolism in the brain. However, direct evidence that apoE plays such a role is lacking. We investigated whether apoE isoforms influence lipid content in the brain. We compared the brains of wild-type mice to apoE knockout (؊/؊) and human apoE3 and apoE4 transgenic mice and compared cerebrospinal fluid (CSF) of humans with different apoE isoforms. We found that there was no effect of apoE on the content of multiple phospholipids, sphingolipids, and cholesterol. There was, however, a marked effect of apoE on the sulfatide (ST) content in both the brain and CSF. The sulfatide mass in hippocampus and cortex of apoE knockout mice was found to be 61 and 114 mol% higher than wild-type mice counterparts at 12 months of age. In contrast, the sulfatide content in brain tissues from human apoE4-expressing mice was ϳ60% less than those found in wild-type mice of the same age. The ST mass in human CSF was significantly dependent on the APOE genotypes of the subjects. Examination of potential sulfatide carrier(s) in human CSF demonstrated that sulfatides are specifically associated with apoEcontaining high density lipoproteins, suggesting that sulfatide levels in the central nervous system (CNS) are likely to be directly modulated by the same metabolic pathways that regulate levels of apoE-containing CNS lipoproteins. This novel role for apoE in the CNS may provide new insights into the connection of apoE with Alzheimer's disease and poor recovery after brain injury.Human apolipoprotein E (apoE, protein; APOE, gene), 1 a 34-kDa protein coded for by a gene on chromosome 19, plays a prominent role in the transport and metabolism of plasma cholesterol and triacylglycerides through its ability to interact with the low density lipoprotein (LDL) receptor and the LDL receptor-related protein (1, 2). It has been postulated that apoE may also play an important role in the redistribution of cholesterol and phospholipids within the central nervous system (CNS) (3) where apoE is expressed mainly in astrocytes (4, 5).In vitro and in vivo data suggest that apoE can play a role in neurite outgrowth and sprouting (4, 6 -9), however, whether this is due to effects on cholesterol and lipid metabolism is unclear. In addition to its role as a plasma lipid transport protein, apoE participates in pathobiological processes, including Alzheimer's disease (AD) (10). The effect of apoE in AD is likely to occur at least in part via interactions with the amyloid-␤ (A␤) peptide (see Ref. 11 for review). To date, the mechanisms of how apoE is involved in all of these biological processes have not been completely clarified.There are three common isoforms of human apoE that differ in amino acids at positions 112 and 158 (1). The most common isoform, apoE3, has cysteine at position 112 and arginine at 158, whereas apoE2 has cysteine at both positions, and apoE4 contains arginine at both positions. The isoforms are encoded by three alleles at the same gene locus. ApoE4 has bee...

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“…There have been several studies demonstrating that a variety of lipid classes are substantially altered at a very early stage during AD pathogenesis (14,15). Furthermore, relative to controls, altered levels of plasma apoE in AD have been observed (16,17).…”

Section: Introductionmentioning

confidence: 99%

Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease

et al. 2014

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Previous studies have shown that mild cognitive impairment (MCI) may be reflective of the early stages of more pronounced neurodegenerative disorders such as Alzheimer's disease (AD). There is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritized for primary preventative measures. The hypothesis was that a minimally invasive approach using cytological markers in isolated buccal mucosa cells can be used to identify individuals of both MCI and AD. An automated buccal cell assay was developed using laser scanning cytometry (LSC) to measure buccal cell type ratios, nuclear DNA content and shape, and neutral lipid content of buccal cells from clinically diagnosed AD (n 5 13) and MCI (n 5 13) patients prior to treatment compared to age-and gender-matched controls (n 5 26). DNA content was significantly higher in all cell types in both MCI (P < 0.01) and AD (P < 0.05) compared with controls mainly due to an increase in >2N nuclei. Abnormal nuclear shape (circularity) was significantly increased in transitional cells in MCI (P < 0.001) and AD (P < 0.01) when compared to controls. In contrast, neutral lipid content (as measured by Oil red O "ORO" staining) of buccal cells was significantly lower in the MCI group (P < 0.05) compared with the control group. The ratio of DNA content/ORO in buccal basal cells for both MCI and AD was significantly higher compared to the control group, with ratios for MCI being approximately 2.8-fold greater (P < 0.01) and AD approximately 2.3-fold greater (P < 0.05) than the control group. Furthermore, there was a strong negative correlation between buccal cell DNA content and ORO content in the AD group (r 2 5 0.75, P < 0.0001) but not in MCI or controls. The changes in the buccal cell cytome observed in this study could prove useful as potential biomarkers in identifying individuals with an increased risk of developing MCI and eventually AD. V C 2014 International Society for Advancement of Cytometry

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Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry

Cited by 510 publications

References 65 publications

Neurolipidomics: challenges and developments

Neurolipidomics: challenges and developments

Novel Role for Apolipoprotein E in the Central Nervous System

Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease

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