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  1. Article ; Online: Apolipoprotein E secreted by astrocytes forms antiparallel dimers in discoidal lipoproteins.

    Strickland, Michael R / Rau, Michael J / Summers, Brock / Basore, Katherine / Wulf, John / Jiang, Hong / Chen, Yun / Ulrich, Jason D / Randolph, Gwendalyn J / Zhang, Rui / Fitzpatrick, James A J / Cashikar, Anil G / Holtzman, David M

    Neuron

    2024  Volume 112, Issue 7, Page(s) 1100–1109.e5

    Abstract: The Apolipoprotein E gene (APOE) is of great interest due to its role as a risk factor for late ...

    Abstract The Apolipoprotein E gene (APOE) is of great interest due to its role as a risk factor for late-onset Alzheimer's disease. ApoE is secreted by astrocytes in the central nervous system in high-density lipoprotein (HDL)-like lipoproteins. Structural models of lipidated ApoE of high resolution could aid in a mechanistic understanding of how ApoE functions in health and disease. Using monoclonal Fab and F(ab')
    MeSH term(s) Astrocytes/metabolism ; Apolipoproteins E/genetics ; Lipoproteins, HDL/chemistry ; Lipoproteins, HDL/metabolism ; Central Nervous System/metabolism ; Apolipoprotein E4/metabolism ; Apolipoprotein E3/metabolism ; Lipoproteins
    Chemical Substances discoidal lipoproteins ; Apolipoproteins E ; Lipoproteins, HDL ; Apolipoprotein E4 ; Apolipoprotein E3 ; Lipoproteins
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2023.12.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Apolipoprotein E O-glycosylation is associated with amyloid plaques and APOE genotype.

    Lawler, Paige E / Bollinger, James G / Schindler, Suzanne E / Hodge, Cynthia R / Iglesias, Nicolas J / Krishnan, Vishal / Coulton, John B / Li, Yan / Holtzman, David M / Bateman, Randall J

    Analytical biochemistry

    2023  Volume 672, Page(s) 115156

    Abstract: Although the APOE ε4 allele is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), the relationship between apolipoprotein (apoE) and AD pathophysiology is not yet fully understood. Relatively little is known about the apoE protein ... ...

    Abstract Although the APOE ε4 allele is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), the relationship between apolipoprotein (apoE) and AD pathophysiology is not yet fully understood. Relatively little is known about the apoE protein species, including post-translational modifications, that exist in the human periphery and CNS. To better understand these apoE species, we developed a LC-MS/MS assay that simultaneously quantifies both unmodified and O-glycosylated apoE peptides. The study cohort included 47 older individuals (age 75.6 ± 5.7 years [mean ± standard deviation]), including 23 individuals (49%) with cognitive impairment. Paired plasma and cerebrospinal fluid samples underwent analysis. We quantified O-glycosylation of two apoE protein residues - one in the hinge region and one in the C-terminal region - and found that glycosylation occupancy of the hinge region in the plasma was significantly correlated with plasma total apoE levels, APOE genotype and amyloid status as determined by CSF Aβ42/Aβ40. A model with plasma glycosylation occupancy, plasma total apoE concentration, and APOE genotype distinguished amyloid status with an AUROC of 0.89. These results suggest that plasma apoE glycosylation levels could be a marker of brain amyloidosis, and that apoE glycosylation may play a role in the pathophysiology of AD.
    MeSH term(s) Aged ; Aged, 80 and over ; Humans ; Alzheimer Disease ; Amyloid beta-Peptides/metabolism ; Apolipoprotein E4/cerebrospinal fluid ; Apolipoprotein E4/genetics ; Apolipoproteins E/genetics ; Apolipoproteins E/metabolism ; Biomarkers/metabolism ; Chromatography, Liquid ; Genotype ; Glycosylation ; Peptide Fragments/metabolism ; Plaque, Amyloid ; Tandem Mass Spectrometry
    Chemical Substances Amyloid beta-Peptides ; Apolipoprotein E4 ; Apolipoproteins E ; Biomarkers ; Peptide Fragments ; ApoE protein, human
    Language English
    Publishing date 2023-04-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1110-1
    ISSN 1096-0309 ; 0003-2697
    ISSN (online) 1096-0309
    ISSN 0003-2697
    DOI 10.1016/j.ab.2023.115156
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Author Correction: Apolipoprotein E controls cerebrovascular integrity via cyclophilin A.

    Bell, Robert D / Winkler, Ethan A / Singh, Itender / Sagare, Abhay P / Deane, Rashid / Wu, Zhenhua / Holtzman, David M / Betsholtz, Christer / Armulik, Annika / Sallstrom, Jan / Berk, Bradford C / Zlokovic, Berislav V

    Nature

    2023  Volume 617, Issue 7961, Page(s) E12

    Language English
    Publishing date 2023-05-04
    Publishing country England
    Document type Published Erratum
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06118-0
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  4. Article ; Online: Correction: Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism.

    Ma, Qingyi / Zhao, Zhen / Sagare, Abhay P / Wu, Yingxi / Wang, Min / Owens, Nelly Chuqui / Verghese, Philip B / Herz, Joachim / Holtzman, David M / Zlokovic, Berislav V

    Molecular neurodegeneration

    2024  Volume 19, Issue 1, Page(s) 27

    Language English
    Publishing date 2024-03-22
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2244557-2
    ISSN 1750-1326 ; 1750-1326
    ISSN (online) 1750-1326
    ISSN 1750-1326
    DOI 10.1186/s13024-024-00716-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Apolipoprotein E O-glycosylation is associated with amyloid plaques and APOE genotype

    Lawler, Paige E. / Bollinger, James G. / Schindler, Suzanne E. / Hodge, Cynthia R. / Iglesias, Nicolas J. / Krishnan, Vishal / Coulton, John B. / Li, Yan / Holtzman, David M. / Bateman, Randall J.

    Analytical Biochemistry. 2023 July, v. 672 p.115156-

    2023  

    Abstract: Although the APOE ε4 allele is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), the relationship between apolipoprotein (apoE) and AD pathophysiology is not yet fully understood. Relatively little is known about the apoE protein ... ...

    Abstract Although the APOE ε4 allele is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), the relationship between apolipoprotein (apoE) and AD pathophysiology is not yet fully understood. Relatively little is known about the apoE protein species, including post-translational modifications, that exist in the human periphery and CNS. To better understand these apoE species, we developed a LC-MS/MS assay that simultaneously quantifies both unmodified and O-glycosylated apoE peptides. The study cohort included 47 older individuals (age 75.6 ± 5.7 years [mean ± standard deviation]), including 23 individuals (49%) with cognitive impairment. Paired plasma and cerebrospinal fluid samples underwent analysis. We quantified O-glycosylation of two apoE protein residues – one in the hinge region and one in the C-terminal region – and found that glycosylation occupancy of the hinge region in the plasma was significantly correlated with plasma total apoE levels, APOE genotype and amyloid status as determined by CSF Aβ42/Aβ40. A model with plasma glycosylation occupancy, plasma total apoE concentration, and APOE genotype distinguished amyloid status with an AUROC of 0.89. These results suggest that plasma apoE glycosylation levels could be a marker of brain amyloidosis, and that apoE glycosylation may play a role in the pathophysiology of AD.
    Keywords Alzheimer disease ; alleles ; amyloid ; amyloidosis ; apolipoprotein E ; brain ; cerebrospinal fluid ; cognitive disorders ; genotype ; glycosylation ; humans ; models ; pathophysiology ; peptides ; risk factors ; standard deviation ; Alzheimer's disease ; Proteomics ; Mass spectrometry
    Language English
    Dates of publication 2023-07
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 1110-1
    ISSN 1096-0309 ; 0003-2697
    ISSN (online) 1096-0309
    ISSN 0003-2697
    DOI 10.1016/j.ab.2023.115156
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Standardized immunoprecipitation protocol for efficient isolation of native apolipoprotein E particles utilizing HJ15.4 monoclonal antibody.

    O'Leary, Justin / Raulin, Ana-Caroline / Li, Zonghua / Martens, Yuka / Inoue, Yasuteru / Strickland, Michael R / Han, Xianlin / Holtzman, David M / Bu, Guojun / Zhao, Na

    STAR protocols

    2023  Volume 4, Issue 2, Page(s) 102271

    Abstract: The apolipoprotein E protein (apoE) confers differential risk for Alzheimer's disease depending ...

    Abstract The apolipoprotein E protein (apoE) confers differential risk for Alzheimer's disease depending on which isoforms are expressed. Here, we present a 2-day immunoprecipitation protocol using the HJ15.4 monoclonal apoE antibody for the pull-down of native apoE particles. We describe major steps for apoE production via immortalized astrocyte culture and HJ15.4 antibody bead coupling for apoE particle pull-down, elution, and characterization. This protocol could be used to isolate native apoE particles from multiple model systems or human biospecimens.
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102271
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  7. Article ; Online: Apolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis.

    Chen, Yun / Strickland, Michael R / Soranno, Andrea / Holtzman, David M

    Neuron

    2020  Volume 109, Issue 2, Page(s) 205–221

    Abstract: Apolipoprotein E (ApoE) is of great interest due to its role as a cholesterol/lipid transporter ...

    Abstract Apolipoprotein E (ApoE) is of great interest due to its role as a cholesterol/lipid transporter in the central nervous system (CNS) and as the most influential genetic risk factor for Alzheimer disease (AD). Work over the last four decades has given us important insights into the structure of ApoE and how this might impact the neuropathology and pathogenesis of AD. In this review, we highlight the history and progress in the structural and molecular understanding of ApoE and discuss how these studies on ApoE have illuminated the physiology of ApoE, receptor binding, and interaction with amyloid-β (Aβ). We also identify future areas of study needed to advance our understanding of how ApoE influences neurodegeneration.
    MeSH term(s) Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Animals ; Apolipoproteins E/chemistry ; Apolipoproteins E/metabolism ; Brain/metabolism ; Brain/pathology ; Humans ; Protein Multimerization/physiology ; Protein Structure, Secondary ; Protein Transport/physiology ; Receptors, LDL/chemistry ; Receptors, LDL/metabolism
    Chemical Substances Apolipoproteins E ; LDLR protein, human ; Receptors, LDL
    Language English
    Publishing date 2020-11-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2020.10.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Standardized immunoprecipitation protocol for efficient isolation of native apolipoprotein E particles utilizing HJ15.4 monoclonal antibody

    Justin O’Leary / Ana-Caroline Raulin / Zonghua Li / Yuka Martens / Yasuteru Inoue / Michael R. Strickland / Xianlin Han / David M. Holtzman / Guojun Bu / Na Zhao

    STAR Protocols, Vol 4, Iss 2, Pp 102271- (2023)

    2023  

    Abstract: Summary: The apolipoprotein E protein (apoE) confers differential risk for Alzheimer’s disease ...

    Abstract Summary: The apolipoprotein E protein (apoE) confers differential risk for Alzheimer’s disease depending on which isoforms are expressed. Here, we present a 2-day immunoprecipitation protocol using the HJ15.4 monoclonal apoE antibody for the pull-down of native apoE particles. We describe major steps for apoE production via immortalized astrocyte culture and HJ15.4 antibody bead coupling for apoE particle pull-down, elution, and characterization. This protocol could be used to isolate native apoE particles from multiple model systems or human biospecimens. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords Cell Biology ; Molecular Biology ; Neuroscience ; Science (General) ; Q1-390
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Correction: Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism.

    Ma, Qingyi / Zhao, Zhen / Sagare, Abhay P / Wu, Yingxi / Wang, Min / Owens, Nelly Chuqui / Verghese, Philip B / Herz, Joachim / Holtzman, David M / Zlokovic, Berislav V

    Molecular neurodegeneration

    2022  Volume 17, Issue 1, Page(s) 71

    Language English
    Publishing date 2022-11-03
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2244557-2
    ISSN 1750-1326 ; 1750-1326
    ISSN (online) 1750-1326
    ISSN 1750-1326
    DOI 10.1186/s13024-022-00573-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Apolipoprotein E and Alzheimer's disease: the influence of apolipoprotein E on amyloid-β and other amyloidogenic proteins.

    Huynh, Tien-Phat V / Davis, Albert A / Ulrich, Jason D / Holtzman, David M

    Journal of lipid research

    2017  Volume 58, Issue 5, Page(s) 824–836

    Abstract: Alzheimer's disease (AD) is one of the fastest-growing causes of death and disability in persons 65 years of age or older, affecting more than 5 million Americans alone. Clinical manifestations of AD include progressive decline in memory, executive ... ...

    Abstract Alzheimer's disease (AD) is one of the fastest-growing causes of death and disability in persons 65 years of age or older, affecting more than 5 million Americans alone. Clinical manifestations of AD include progressive decline in memory, executive function, language, and other cognitive domains. Research efforts within the last three decades have identified
    MeSH term(s) Alzheimer Disease/metabolism ; Amyloid beta-Peptides/biosynthesis ; Amyloid beta-Peptides/chemistry ; Amyloid beta-Peptides/metabolism ; Animals ; Apolipoproteins E/metabolism ; Humans ; Risk Factors
    Chemical Substances Amyloid beta-Peptides ; Apolipoproteins E
    Language English
    Publishing date 2017-02-27
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 80154-9
    ISSN 1539-7262 ; 0022-2275
    ISSN (online) 1539-7262
    ISSN 0022-2275
    DOI 10.1194/jlr.R075481
    Database MEDical Literature Analysis and Retrieval System OnLINE

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