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Cited by 12Alzheimer's disease research and treatmentsCholesterol and Lipid MetabolismMetabolomics and Mass Spectrometry Studies

Neurometabolic roles of ApoE and Ldl-R in mouse brain

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Lee, Jieun, Choi, Joseph, Wong, G. William, Wolfgang, Michael J.·2016·Journal of Bioenergetics and Biomembranes
DOI 10.1007/s10863-015-9636-6PMC PMC4733629
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Abstract

Polymorphisms in ApoE are highly correlated with the progression of neurodegenerative disease, in particular Alzheimer's disease. Little is known, however, about the role of ApoE or cholesterol metabolism on brain neurochemistry in general. To better understand the role of lipoprotein and cholesterol metabolism in the brain, we profiled 6 and 12-week old Apoe KO and Ldlr KO mouse models via unbiased metabolomics to determine which metabolites were affected at an early age to identify those that may play a role in triggering pathology later in life. Steady-state metabolomics revealed only subtle differences among Apoe KO, Ldlr KO and WT mouse brains. Ldlr KO mice exhibited alterations in metabolites involved in neurotransmitter, amino acid and cholesterol metabolism. In contrast, Apoe KO mice only showed subtle changes in amino acid and neurotransmitter metabolism. These subtle changes in a broad range of metabolites indicate that ApoE and Ldl-R alone may not play a significant role in these mouse models at an early age, but instead require the cumulative effect from different pathways that lead to dysfunction at a much later stage of life.

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  • The absence of LDLR or ApoE elevated serum cholesterol dramatically while having very subtle effects on fatty acids or lipid metabolism in the brain.

    “The absence of LDLR or ApoE elevated the serum cholesterol dramatically while having very subtle effects on the fatty acids or lipids metabolism in the brain [45].”

    From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [45]

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  1. [1]Wegener G Brains burning fat: different forms of energy metabolism in the CNS of insects Naturwissenschaften 1983 70 43 45 6843678
  2. [2]Canevari L Clark JB Alzheimer's disease and cholesterol: the fat connection Neurochemical research 2007 32 739 750 17191138
  3. [3]Fryer JD Demattos RB McCormick LM O'Dell MA Spinner ML Bales KR Paul SM Sullivan PM Parsadanian M Bu G Holtzman DM The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice The Journal of biological chemistry 2005 280 25754 25759 15888448
  4. [4]Cheng H Wang M Li JL Cairns NJ Han X Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer's disease: an early event in disease pathogenesis Journal of neurochemistry 2013 127 733 738 23865640 PMC3844035
  5. [5]Cheng H Zhou Y Holtzman DM Han X Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer's disease Neurobiology of aging 2010 31 1188 1196 18762354 PMC2873070
  6. [6]Han X The role of apolipoprotein E in lipid metabolism in the central nervous system Cellular and molecular life sciences: CMLS 2004 61 1896 1906 15289932 PMC11138510
  7. [8]Han X Rozen S Boyle SH Hellegers C Cheng H Burke JR Welsh-Bohmer KA Doraiswamy PM Kaddurah-Daouk R Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics PloS one 2011 6 e21643 21779331 PMC3136924
  8. [9]Burgess BL McIsaac SA Naus KE Chan JY Tansley GH Yang J Miao F Ross CJ van Eck M Hayden MR van Nostrand W St George-Hyslop P Westaway D Wellington CL Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma Neurobiology of disease 2006 24 114 127 16899370
  9. [10]Russell DW Halford RW Ramirez DM Shah R Kotti T Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain Annu Rev Biochem 2009 78 1017 1040 19489738 PMC2837268
  10. [11]Kaliyamurthi V Thanigavelan V Rajamanickam GV Effects of diet-induced hypercholesterolemia on amyloid accumulation in ovariectomized mice Journal of biosciences 2012 37 1017 1027 23151792
  11. [12]Wisniewski T Newman K Javitt NB Alzheimer's disease: brain desmosterol levels Journal of Alzheimer's disease: JAD 2013 33 881 888 23042211 PMC3557460
  12. [13]Hartmann T Kuchenbecker J Grimm MO Alzheimer's disease: the lipid connection Journal of neurochemistry 2007 103 Suppl 1 159 170 17986151
  13. [14]Rebeck GW LaDu MJ Estus S Bu G Weeber EJ The generation and function of soluble apoE receptors in the CNS Molecular neurodegeneration 2006 1 15 17062143 PMC1635701
  14. [15]Orth M Bellosta S Cholesterol: its regulation and role in central nervous system disorders Cholesterol 2012 2012 292598 23119149 PMC3483652
  15. [16]Fan QW Iosbe I Asou H Yanagisawa K Michikawa M Expression and regulation of apolipoprotein E receptors in the cells of the central nervous system in culture: A review Journal of the American Aging Association 2001 24 1 10 23604870 PMC3455648
  16. [17]Mulder M Jansen PJ Janssen BJ van de Berg WD van der Boom H Havekes LM de Kloet RE Ramaekers FC Blokland A Low-density lipoprotein receptor-knockout mice display impaired spatial memory associated with a decreased synaptic density in the hippocampus Neurobiology of disease 2004 16 212 219 15207278
  17. [18]Puglielli L Tanzi RE Kovacs DM Alzheimer's disease: the cholesterol connection Nature neuroscience 2003 6 345 351 12658281
  18. [19]Wahrle SE Jiang H Parsadanian M Legleiter J Han X Fryer JD Kowalewski T Holtzman DM ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE The Journal of biological chemistry 2004 279 40987 40993 15269217
  19. [20]Spencer BJ Verma IM Targeted delivery of proteins across the blood-brain barrier Proceedings of the National Academy of Sciences of the United States of America 2007 104 7594 7599 17463083 PMC1857226
  20. [21]Eckel-Mahan KL Patel VR Mohney RP Vignola KS Baldi P Sassone-Corsi P Coordination of the transcriptome and metabolome by the circadian clock Proceedings of the National Academy of Sciences of the United States of America 2012 109 5541 5546 22431615 PMC3325727
  21. [22]Ellis JM Wong GW Wolfgang MJ Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity Molecular and cellular biology 2013 33 1869 1882 23459938 PMC3624175
  22. [23]Lee J Wolfgang MJ Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism BMC biochemistry 2012 13 23 23098614 PMC3523003
  23. [24]Wolfgang MJ Kurama T Dai Y Suwa A Asaumi M Matsumoto S Cha SH Shimokawa T Lane MD The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis Proceedings of the National Academy of Sciences of the United States of America 2006 103 7282 7287 16651524 PMC1564279
  24. [25]Pendse AA Arbones-Mainar JM Johnson LA Altenburg MK Maeda N Apolipoprotein E knock-out and knock-in mice: atherosclerosis, metabolic syndrome, and beyond Journal of lipid research 2009 50 Suppl S178 S182 19060252 PMC2674752
  25. [26]Alakbarzade V Hameed A Quek DQ Chioza BA Baple EL Cazenave-Gassiot A Nguyen LN Wenk MR Ahmad AQ Sreekantan-Nair A Weedon MN Rich P Patton MA Warner TT Silver DL Crosby AH A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome Nat Genet 2015 26005865
  26. [28]Hogyes E Nyakas C Kiliaan A Farkas T Penke B Luiten PG Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats Neuroscience 2003 119 999 1012 12831859
  27. [29]Soderberg M Edlund C Kristensson K Dallner G Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease Lipids 1991 26 421 425 1881238
  28. [30]Tully AM Roche HM Doyle R Fallon C Bruce I Lawlor B Coakley D Gibney MJ Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study The British journal of nutrition 2003 89 483 489 12654166
  29. [31]Panula P Rinne J Kuokkanen K Eriksson KS Sallmen T Kalimo H Relja M Neuronal histamine deficit in Alzheimer's disease Neuroscience 1998 82 993 997 9466423
  30. [32]Trushina E Dutta T Persson XM Mielke MM Petersen RC Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer's disease using metabolomics PloS one 2013 8 e63644 23700429 PMC3658985
  31. [33]Kaether C Haass C A lipid boundary separates APP and secretases and limits amyloid beta-peptide generation The Journal of cell biology 2004 167 809 812 15583026 PMC2172467
  32. [35]Lim GP Calon F Morihara T Yang F Teter B Ubeda O Salem N Jr Frautschy SA Cole GM A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model J Neurosci 2005 25 3032 3040 15788759 PMC6725084
  33. [36]Oksman M Iivonen H Hogyes E Amtul Z Penke B Leenders I Broersen L Lutjohann D Hartmann T Tanila H Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice Neurobiology of disease 2006 23 563 572 16765602
  34. [37]Haas HL Sergeeva OA Selbach O Histamine in the nervous system Physiological reviews 2008 88 1183 1241 18626069
  35. [38]Nuutinen S Panula P Histamine in neurotransmission and brain diseases Advances in experimental medicine and biology 2010 709 95 107 21618891
  36. [39]Bhowmik M Khanam R Vohora D Histamine H3 receptor antagonists in relation to epilepsy and neurodegeneration: a systemic consideration of recent progress and perspectives British journal of pharmacology 2012 167 1398 1414 22758607 PMC3514756

Cited by

Sorted by citations

Authors
Lee, J., Choi, J., Wong, G. W., & Wolfgang, M. J.
Affiliations
Johns Hopkins University (US)
Corresponding author
Wolfgang, Michael J.
ORCID
Venue
Journal of Bioenergetics and Biomembranes
Publisher
Springer Science and Business Media LLC
Published
2015-12-21
Volume
48
Issue
1
Pages
13-21
ISSN
  • 0145-479X (ISSN-L)
  • 1573-6881
DOI
10.1007/s10863-015-9636-6
PMC
PMC4733629
OpenAlex
W2253378164
Cited by
12
References
3
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2018: 1 · 2016: 3
FWCI
0.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Bioenergetics and Biomembranes (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (NS072241)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK084171)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
apolipoprotein E, LDL receptor, brain metabolomics, cholesterol metabolism, lipoprotein metabolism, ApoE-deficient mice, Ldlr knockout mice, neurotransmitter metabolism, amino acid metabolism, neurodegeneration, Alzheimer's disease, brain neurochemistry
MeSH terms
Animals, Apolipoproteins E, Brain, Cholesterol, Nerve Tissue Proteins, Receptors, LDL, Mice, Knockout, Mice

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