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Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein/tau for Alzheimer’s disease

Tajima, Yoko, Ishikawa, Masaki, Maekawa, Keiko, Murayama, Mayumi, Senoo, Yuya, Nishimaki-Mogami, Tomoko, Nakanishi, Hiroki, Ikeda, Kazutaka, Arita, Makoto, Taguchi, Ryo, Okuno, Alato, Mikawa, Ryuta, Niida, Shumpei, Takikawa, Osamu, Saito, Yoshiro·2013·Lipids in Health and Disease
DOI 10.1186/1476-511x-12-68PMC PMC3668217
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Abstract

Background: Alzheimer’s disease (AD), the most common cause of dementia among neurodegenerative diseases, afflicts millions of elderly people worldwide. In addition to amyloid-beta (Aβ) peptide and phosphorylated tau, lipid dysregulation is suggested to participate in AD pathogenesis. However, alterations in individual lipid species and their role in AD disease progression remain unclear. Methods: We performed a lipidomic analysis using brain tissues and plasma obtained from mice expressing mutated human amyloid precursor protein (APP) and tau protein (Tg2576×JNPL3) (APP/tau mice) at 4 (pre-symptomatic phase), 10 (early symptomatic) and 15 months (late symptomatic). Results: Levels of docosahexaenoyl (22:6) cholesterol ester (ChE) were markedly increased in APP/tau mice compared to controls at all stages examined. Several species of ethanolamine plasmalogens (pPEs) and sphingomyelins (SMs) showed different levels between brains from APP/tau and control mice at various stages of AD. Increased levels of 12-hydroxyeicosatetraenoic acid (12-HETE) during the early symptomatic phase were consistent with previous reports using human AD brain tissue. In addition, 19,20-dihydroxy-docosapentaenoic acid (19,20-diHDoPE) and 17,18-dihydroxy-eicosatetraenoic acid (17,18-diHETE), which are produced from docosahexaenoic acid and eicosapentaenoic acid via 19,20-epoxy-docosapentaenoic acid (19,20-EpDPE) and 17,18-epoxy-eicosatetraenoic acid (17,18-EpETE), respectively, were significantly increased in APP/tau brains during the pre-symptomatic phase, and concomitant increases occurred in plasma. Several arachidonic acid metabolites such as prostaglandin D 2 (PGD 2) and 15-hydroxyeicosatetraenoic acid (15-HETE), which have potential deteriorating and protective actions, respectively, were decreased in the early symptomatic phase of APP/tau mice. Significant decreases in phosphatidylcholines and PEs with polyunsaturated fatty acids were also detected in the late symptomatic phase, indicating a perturbation of membrane properties. Conclusion: Our results provide fundamental information on lipid dysregulation during various stages of human AD.

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Crossref · 10.1186/1476-511x-12-68

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  • CE accumulate in FAD and SAD.

    “In addition to increased Aβ and pTau levels, CE also accumulate in FAD and SAD.”

    From Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-β in iPSC-Derived Alzheimer’s Disease Neurons (2019) · cites this paper as Tajima et al., 2013

    The Results (Analysis of brain tissues; page not provided) report increased cholesterol ester in APP/tau mouse brains, and the Background reports cholesterol-ester enrichment in postmortem brains from patients with late-onset AD. The paper does not establish accumulation specifically in human familial AD (FAD) and sporadic AD (SAD) as separate groups; its direct finding is from a mouse model. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Changes in CE, induced by APP mutations or SAD genetic risk variants in APP, could contribute to Tau pathology.

    “Our findings provide a mechanistic explanation for how changes in CE, induced by APP mutations or SAD genetic risk variants in APP (Chan et al., 2012, Tajima et al., 2013, Yang et al., 2014) could contribute to Tau pathology.”

    From Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-β in iPSC-Derived Alzheimer’s Disease Neurons (2019) · cites this paper as Tajima et al., 2013

    The Results report increased 22:6 cholesterol ester in APP/tau mice compared with controls. The Animals section shows that these mice carried both mutant APP and mutant tau, so the study does not isolate the effect of APP mutations; it also does not examine sporadic Alzheimer’s disease risk variants in APP. The proposed contribution to tau pathology is the citing authors’ own interpretation, not a finding established by this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Brains of AD patients and familial AD-transgenic mice have elevated cholesterol levels.

    “In addition, brains of AD patients [9] and familial AD-transgenic (FAD-Tg) mice [4, 5] have elevated cholesterol levels.”

    From Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation (2023) · cites this paper as [5]

    The citation to this paper is attached to the claim about familial AD-transgenic mice. The Results and Discussion report increased brain levels of a specific cholesterol ester, 22:6ChE, in APP/tau mice compared with controls. They do not establish that overall brain cholesterol levels were elevated; the AD-patient portion of the sentence is attributed to a different citation. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Accumulation of neutral lipids, particularly cholesteryl esters and triacylglycerol stored as lipid droplets, is found in aged and AD brains.

    “Accumulation of neutral lipids, particularly cholesteryl esters (CE) and triacylglycerol (TAG) stored as lipids droplets (LD), is found in aged and AD brains [4–8].”

    From Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation (2023) · cites this paper as [5]

    The Results (Analysis of brain tissues; page not provided) report increased cholesterol ester in APP/tau mouse brains and an increase in one triacylglycerol species at 10 months. They also report that most triacylglycerols were decreased at 15 months. The paper does not establish neutral-lipid accumulation in normal aged brains or show that these lipids were stored in lipid droplets. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Multiple AD mouse models show 3- to 11-fold higher CE levels in the brain compared to controls.

    “Additionally, multiple AD mouse models have shown 3‐ to 11‐fold higher CE levels in the brain compared to controls. 7 , 8”

    From Inhibition of Acyl‐CoenzymeA: Cholesterol Acyltransferase 1 promotes shedding of soluble triggering receptor on myeloid cells 2 (TREM2) and low‐density lipoprotein receptor 1 (LRP1)‐dependent phagocytosis of amyloid beta protein in microglia (2025) · cites this paper as [8]

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Research works printed but not linked: 32

  1. Tanzi RE, Bertram L: Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell. 2005, 120: 545-555. 10.1016/j.cell.2005.02.008 · DOI · Paper page
  2. Cummings JL: Alzheimer's disease. N Engl J Med. 2004, 351: 56-67. 10.1056/NEJMra040223 · DOI · Paper page
  3. Osenkowski P, Ye W, Wang R, Wolfe MS, Selkoe DJ: Direct and potent regulation of gamma-secretase by its lipid microenvironment. J Biol Chem. 2008, 283: 22529-22540. 10.1074/jbc.M801925200 · DOI
  4. Holmes O, Paturi S, Ye W, Wolfe MS, Selkoe DJ: Effects of membrane lipids on the activity and processivity of purified gamma-secretase. Biochemistry. 2012, 51: 3565-3575. 10.1021/bi300303g · DOI
  5. Umeda T, Tomiyama T, Kitajima E, Idomoto T, Nomura S, Lambert MP, Klein WL, Mori H: Hypercholesterolemia accelerates intraneuronal accumulation of Abeta oligomers resulting in memory impairment in Alzheimer's disease model mice. Life Sci. 2012, 91: 1169-1176. 10.1016/j.lfs.2011.12.022 · DOI
  6. Calon F: Omega-3 polyunsaturated fatty acids in Alzheimer's disease: key questions and partial answers. Curr Alzheimer Res. 2011, 8: 470-478. 10.2174/156720511796391881 · DOI
  7. Cunnane SC, Schneider JA, Tangney C, Tremblay-Mercier J, Fortier M, Bennett DA, Morris MC: Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis. 2012, 29: 691-697. · DOI
  8. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG: A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest. 2005, 115: 2774-2783. 10.1172/JCI25420 · DOI
  9. Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, Yen SH, Sahara N, Skipper L, Yager D, Eckman C, Hardy J, Hutton M, McGowan E: Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science. 2001, 293: 1487-1491. 10.1126/science.1058189 · DOI · Paper page
  10. Taguchi R, Ishikawa M: Precise and global identification of phospholipid molecular species by an Orbitrap mass spectrometer and automated search engine Lipid Search. J Chromatogr A. 2010, 1217: 4229-4239. 10.1016/j.chroma.2010.04.034 · DOI
  11. Ishikawa M, Tajima Y, Murayama M, Senoo Y, Maekawa K, Saito Y: Plasma and serum from nonfasting men and women differ in their lipidomic profiles. Biol Pharm Bull. 2013, 36: 682-685. 10.1248/bpb.b12-00799 · DOI
  12. Ono M, Shitashige M, Honda K, Isobe T, Kuwabara H, Matsuzuki H, Hirohashi S, Yamada T: Label-free quantitative proteomics using large peptide data sets generated by nanoflow liquid chromatography and mass spectrometry. Mol Cell Proteomics. 2006, 5: 1338-1347. 10.1074/mcp.T500039-MCP200 · DOI
  13. Bhattacharyya R, Kovacs DM: ACAT inhibition and amyloid beta reduction. Biochim Biophys Acta. 2010, 1801: 960-965. 10.1016/j.bbalip.2010.04.003 · DOI · Paper page
  14. Ginsberg L, Rafique S, Xuereb JH, Rapoport SI, Gershfeld NL: Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer's disease brain. Brain Res. 1995, 698: 223-226. 10.1016/0006-8993(95)00931-F · DOI
  15. Han X, Holtzman DM, McKeel DW: Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J Neurochem. 2001, 77: 1168-1180. 10.1046/j.1471-4159.2001.00332.x · DOI
  16. Rothhaar TL, Grosgen S, Haupenthal VJ, Burg VK, Hundsdorfer B, Mett J, Riemenschneider M, Grimm HS, Hartmann T, Grimm MO: Plasmalogens inhibit APP processing by directly affecting gamma-secretase activity in Alzheimer's disease. Scientific World Journal. 2012, 2012: 141240- · DOI
  17. Grimm MO, Kuchenbecker J, Rothhaar TL, Grosgen S, Hundsdorfer B, Burg VK, Friess P, Müller U, Grimm HS, Riemenschneider M, Hartmann T: Plasmalogen synthesis is regulated via alkyl-dihydroxyacetonephosphate-synthase by amyloid precursor protein processing and is affected in Alzheimer's disease. J Neurochem. 2011, 116: 916-925. 10.1111/j.1471-4159.2010.07070.x · DOI
  18. Praticò D, Zhukareva V, Yao Y, Uryu K, Funk CD, Lawson JA, Trojanowski JQ, Lee VM: 12/15-lipoxygenase is increased in Alzheimer's disease: possible involvement in brain oxidative stress. Am J Pathol. 2004, 164: 1655-1662. 10.1016/S0002-9440(10)63724-8 · DOI
  19. Piomelli D, Volterra A, Dale N, Siegelbaum SA, Kandel ER, Schwartz JH, Belardetti F: Lipoxygenase metabolites of arachidonic acid as second messengers for presynaptic inhibition of Aplysia sensory cells. Nature. 1987, 328: 38-43. 10.1038/328038a0 · DOI
  20. Svennerholm L, Gottfries CG: Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demyelination in late-onset form (type II). J Neurochem. 1994, 62: 1039-1047. · DOI
  21. Grimm MO, Grimm HS, Patzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, De Strooper B, Muller U, Shen J, Hartmann T: Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nat Cell Biol. 2005, 7: 1118-1123. 10.1038/ncb1313 · DOI
  22. Bate C, Kempster S, Williams A: Prostaglandin D2 mediates neuronal damage by amyloid-beta or prions which activates microglial cells. Neuropharmacology. 2006, 50: 229-237. 10.1016/j.neuropharm.2005.09.008 · DOI
  23. Khandelwal PJ, Herman AM, Moussa CE: Inflammation in the early stages of neurodegenerative pathology. J Neuroimmunol. 2011, 238: 1-11. 10.1016/j.jneuroim.2011.07.002 · DOI
  24. Shappell SB, Gupta RA, Manning S, Whitehead R, Boeglin WE, Schneider C, Case T, Price J, Jack GS, Wheeler TM, Matusik RJ, Brash AR, Dubois RN: 15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells. Cancer Res. 2001, 61: 497-503.
  25. Iliff JJ, Jia J, Nelson J, Goyagi T, Klaus J, Alkayed NJ: Epoxyeicosanoid signaling in CNS function and disease. Prostaglandins Other Lipid Mediat. 2010, 91: 68-84. 10.1016/j.prostaglandins.2009.06.004 · DOI
  26. Shin JH, Engidawork E, Delabar JM, Lubec G: Identification and characterisation of soluble epoxide hydrolase in mouse brain by a robust protein biochemical method. Amino Acids. 2005, 28: 63-69. 10.1007/s00726-004-0145-x · DOI
  27. Hercule HC, Salanova B, Essin K, Honeck H, Falck JR, Sausbier M, Ruth P, Schunck WH, Luft FC, Gollasch M: The vasodilator 17, 18-epoxyeicosatetraenoic acid targets the pore-forming BK alpha channel subunit in rodents. Exp Physiol. 2007, 92: 1067-1076. 10.1113/expphysiol.2007.038166 · DOI
  28. Shah NS, Vidal JS, Masaki K, Petrovitch H, Ross GW, Tilley C, DeMattos RB, Tracy RP, White LR, Launer LJ: Midlife blood pressure, plasma beta-amyloid, and the risk for Alzheimer disease: the Honolulu Asia Aging Study. Hypertension. 2012, 59: 780-786. 10.1161/HYPERTENSIONAHA.111.178962 · DOI
  29. Morin C, Sirois M, Echave V, Albadine R, Rousseau E: 17, 18-epoxyeicosatetraenoic acid targets PPARγ and p38 mitogen-activated protein kinase to mediate its anti-inflammatory effects in the lung: role of soluble epoxide hydrolase. Am J Respir Cell Mol Biol. 2010, 43: 564-575. 10.1165/rcmb.2009-0155OC · DOI
  30. Liu M, Sun A, Shin EJ, Liu X, Kim SG, Runyons CR, Markesbery W, Kim HC, Bing G: Expression of microsomal epoxide hydrolase is elevated in Alzheimer's hippocampus and induced by exogenous beta-amyloid and trimethyl-tin. Eur J Neurosci. 2006, 23: 2027-2034. 10.1111/j.1460-9568.2006.04724.x · DOI
  31. Lagarde M, Bernoud N, Brossard N, Lemaitre-Delaunay D, Thiès F, Croset M, Lecerf J: Lysophosphatidylcholine as a preferred carrier form of docosahexaenoic acid to the brain. J Mol Neurosci. 2001, 16: 201-204. discussion 215–221, 10.1385/JMN:16:2-3:201 · DOI
  32. Goodenowe DB, Cook LL, Liu J, Lu Y, Jayasinghe DA, Ahiahonu PW, Heath D, Yamazaki Y, Flax J, Krenitsky KF, Sparks DL, Lerner A, Friedland RP, Kudo T, Kamino K, Morihara T, Takeda M, Wood PL: Peripheral ethanolamine plasmalogen deficiency: a logical causative factor in Alzheimer's disease and dementia. J Lipid Res. 2007, 48: 2485-2498. 10.1194/jlr.P700023-JLR200 · DOI

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Metadata

Authors
Tajima, Y., Ishikawa, M., Maekawa, K., Murayama, M., Senoo, Y., Nishimaki-Mogami, T., Nakanishi, H., Ikeda, K., Arita, M., Taguchi, R., Okuno, A., Mikawa, R., Niida, S., Takikawa, O., & Saito, Y.
Venue
Lipids in Health and Disease
Publisher
Springer Science and Business Media LLC
Published
2013-05-09
Volume
12
Issue
1
ISSN
1476-511X
DOI
10.1186/1476-511x-12-68
PMC
PMC3668217
Cited by
139
References
4
Language
en

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