Lipidomic Profiles in Diabetes and Dementia

Journal of Alzheimer's Disease

Volumn 59, Issue 2, 2017, Pages 433-444

  Huynh, Kevin ^a,b   Martins, Ralph N ^c,d   Meikle, Peter J ^a,b  

^a BAKER IDI HEART AND DIABETES INSTITUTE   (Australia)

^b MONASH UNIVERSITY   (Australia)

^c EDITH COWAN UNIVERSITY   (Australia)

^d MACQUARIE UNIVERSITY   (Australia)

Author keywords

Alzheimer's disease; diabetes mellitus; lipid metabolism; mass spectrometry; risk

Indexed keywords

APOLIPOPROTEIN E; CERAMIDE; PLASMALOGEN; SULFATIDE; LIPID;

DEMENTIA; DIABETES MELLITUS; DISEASE ASSOCIATION; EXOSOME; FAT INTAKE; HUMAN; INSULIN RESISTANCE; LIPID ANALYSIS; LIPID METABOLISM; LIPIDOMICS; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; ANIMAL; CHEMISTRY; METABOLISM; PATHOLOGY;

ANIMALS; DEMENTIA; DIABETES MELLITUS; HUMANS; LIPID METABOLISM; LIPIDS;

EID: 85024859813     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-161215     Document Type: Review

References (107)

1. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103, 137-149.
2. Daneman D (2006) Type 1 diabetes. Lancet 367, 847-858.
3. Leahy JL (2005) Pathogenesis of type 2 diabetes mellitus. Arch Med Res 36, 197-209.
4. Mooradian AD (2009) Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab 5, 150-159.
5. Ehehalt R, Keller P, Haass C, Thiele C, Simons K (2003) Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts. J Cell Biol 160, 113-123.
6. Cordy JM, Hussain I, Dingwall C, Hooper NM, Turner AJ (2003) Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. Proc Natl Acad Sci U S A 100, 11735-11740.
7. Vetrivel KS, Thinakaran G (2010) Membrane rafts in Alzheimer's disease beta-amyloid production. Biochim Biophys Acta 1801, 860-867.
8. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's Disease: Progress and problems on the road to therapeutics. Science 297, 353-356.
9. Scarmeas N, Stern Y, Tang M-X, Mayeux R, Luchsinger JA (2006) Mediterranean diet and risk for Alzheimer's disease. Ann Neurol 59, 912-921.
10. Querfurth HW, LaFerla FM (2010) Alzheimer's Disease. N Engl J Med 362, 329-344.
11. Corder E, Saunders A, Strittmatter W, Schmechel D, Gaskell P, Small G, Roses A, Haines J, Pericak-Vance M (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261, 921-923.
12. Stewart R, Liolitsa D (1999) Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 16, 93-112.
13. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P (2006) Risk of dementia in diabetes mellitus: A systematic review. Lancet Neurol 5, 64-74.
14. Ott A, Stolk R, Van Harskamp F, Pols H, Hofman A, Breteler M (1999) Diabetes mellitus and the risk of dementia The Rotterdam Study. Neurology 53, 1937-1942.
15. Peila R, Rodriguez BL, Launer LJ; Honolulu-Asia Aging Study (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies. Diabetes 51, 1256-1262.
16. Whitmer RA (2007) Type 2 diabetes and risk of cognitive impairment and dementia. Curr Neurol Neurosci Rep 7, 373-380.
17. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease-is this type 3 diabetes? J Alzheimers Dis 7, 63-80.
18. Schubert M, Gautam D, Surjo D, Ueki K, Baudler S, Schubert D, Kondo T, Alber J, Galldiks N, Kustermann E, Arndt S, Jacobs AH, Krone W, Kahn CR, Bruning JC (2004) Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci U S A 101, 3100-3105.
19. Hwang LL, Wang CH, Li TL, Chang SD, Lin LC, Chen CP, Chen CT, Liang KC, Ho IK, Yang WS, Chiou LC (2010) Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice. Obesity (Silver Spring) 18, 463-469.
20. Farr SA, Yamada KA, Butterfield DA, Abdul HM, Xu L, Miller NE, Banks WA, Morley JE (2008) Obesity and hypertriglyceridemia produce cognitive impairment. Endocrinology 149, 2628-2636.
21. Saltiel AR, Kahn CR (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414, 799-806.
22. Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, Bandyopadhyay S, Jones KN, Kelly S, Shaner RL, Sullards CM, Wang E, Murphy RC, Barkley RM, Leiker TJ, Raetz CR, Guan Z, Laird GM, Six DA, Russell DW, McDonald JG, Subramaniam S, Fahy E, Dennis EA (2010) Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res 51, 3299-3305.
23. Fahy E, Subramaniam S, Brown HA, Glass CK, Merrill AH, Murphy RC, Raetz CR, RussellDW, SeyamaY, Shaw W, Shimizu T, Spener F, van Meer G, Van Nieuwenhze MS, White SH, Witztum JL, Dennis EA (2005) A comprehensive classification system for lipids. J Lipid Res 46, 839-861.
24. Fahy E, Subramaniam S, Murphy RC, Nishijima M, Raetz CR, Shimizu T, Spener F, van Meer G, Wakelam MJ, Dennis EA (2009) Update of the LIPID MAPS comprehensive classification system for lipids. J Lipid Res 50, S9-S14.
25. Hyötyläinen T, Orešič M (2015) Optimizing the lipidomics workflow for clinical studies-practical considerations. Anal Bioanal Chem 407, 4973-4993.
26. Wang C, Wang M, Han X (2015) Applications of mass spectrometry for cellular lipid analysis. Mol Biosyst 11, 698-713.
27. Zhao Y-Y, Wu S-P, Liu S, Zhang Y, Lin R-C (2014) Ultraperformance liquid chromatography-mass spectrometry as a sensitive and powerful technology in lipidomic applications. Chem Biol Interact 220, 181-192.
28. Meikle PJ, Wong G, Barlow CK, Kingwell BA (2014) Lipidomics: Potential role in risk prediction and therapeutic monitoring for diabetes and cardiovascular disease. Pharmacol Ther 143, 12-23.
29. Haus JM, Kashyap SR, Kasumov T, Zhang R, Kelly KR, Defronzo RA, Kirwan JP (2009) Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58, 337-343.
30. Lopez X, Goldfine AB, Holland WL, Gordillo R, Scherer PE (2013) Plasma ceramides are elevated in female children and adolescents with type 2 diabetes. J Pediatr Endocrinol Metab 26, 995-998.
31. Boon J, Hoy AJ, Stark R, Brown RD, Meex RC, Henstridge DC, Schenk S, Meikle PJ, Horowitz JF, Kingwell BA, Bruce CR, Watt MJ (2013) Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance. Diabetes 62, 401-410.
32. Coen PM, Hames KC, Leachman EM, DeLany JP, Ritov VB, Menshikova EV, Dube JJ, Stefanovic-Racic M, Toledo FG, Goodpaster BH (2013) Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity. Obesity (Silver Spring) 21, 2362-2371.
33. Coen PM, Dubé JJ, Amati F, Stefanovic-Racic M, Ferrell RE, Toledo FG, Goodpaster BH (2010) Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes 59, 80-88.
34. Meikle PJ, Wong G, Barlow CK, Weir JM, Greeve MA, MacIntosh GL, Almasy L, Comuzzie AG, Mahaney MC, Kowalczyk A, Haviv I, Grantham N, Magliano DJ, Jowett JB, Zimmet P, Curran JE, Blangero J, Shaw J (2013) Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes. PLoS One 8, e74341.
35. Kennedy EP, Weiss SB (1956) The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem 222, 193-214.
36. Vance DE, Ridgway ND (1988) The methylation of phosphatidylethanolamine. Prog Lipid Res 27, 61-79.
37. Weir JM, Wong G, Barlow CK, Greeve MA, Kowalczyk A, Almasy L, Comuzzie AG, Mahaney MC, Jowett JB, Shaw J, Curran JE, Blangero J, Meikle PJ (2013) Plasma lipid profiling in a large population-based cohort. J Lipid Res 54, 2898-2908.
38. Arendt BM, Ma DW, Simons B, Noureldin SA, Therapondos G, Guindi M, Sherman M, Allard JP (2013) Nonalcoholic fatty liver disease is associated with lower hepatic and erythrocyte ratios of phosphatidylcholine to phosphatidylethanolamine. Appl Physiol Nutr Metab 38, 334-340.
39. Li Z, Agellon LB, Allen TM, Umeda M, Jewell L, Mason A, Vance DE (2006) The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab 3, 321-331.
40. Levy M, Futerman AH (2010) Mammalian ceramide synthases. IUBMB life 62, 347-356.
41. Reynolds CP, Maurer BJ, Kolesnick RN (2004) Ceramide synthesis and metabolism as a target for cancer therapy. Cancer Lett 206, 169-180.
42. Chaurasia B, Summers SA (2015) Ceramides-lipotoxic inducers of metabolic disorders. Trends Endocrinol Metab 26, 538-550.
43. Schubert KM, Scheid MP, Duronio V (2000) Ceramide inhibits protein kinase B/Akt by promoting dephosphorylation of serine 473. J Biol Chem 275, 13330-13335.
44. Summers SA, Garza LA, Zhou H, Birnbaum MJ (1998) Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide. Mol Cell Biol 18, 5457-5464.
45. Brites P, Waterham HR, Wanders RJA (2004) Functions and biosynthesis of plasmalogens in health and disease. Biochim Biophys Acta 1636, 219-231.
46. Denimal D, Nguyen A, Pais de Barros J-P, Bouillet B, Petit J-M, Vergès B, Duvillard L (2016) Major changes in the sphingophospholipidome of HDL in non-diabetic patients with metabolic syndrome. Atherosclerosis 246, 106-114.
47. Lessig J, Fuchs B (2009) Plasmalogens in biological systems: Their role in oxidative processes in biological membranes, their contribution to pathological processes and aging and plasmalogen analysis. Curr Med Chem 16, 2021-2041.
48. Wallner S, Schmitz G (2011) Plasmalogens the neglected regulatory and scavenging lipid species. Chem Phys Lipids 164, 573-589.
49. Mankidy R, Ahiahonu PWK, Ma H, Jayasinghe D, Ritchie SA, Khan MA, Su-Myat KK, Wood PL, Goodenowe DB (2010) Membrane plasmalogen composition and cellular cholesterol regulation: A structure activity study. Lipids Health Dis 9, 1-62.
50. Hossain MS, Ifuku M, Take S, Kawamura J, Miake K, Katafuchi T (2013) Plasmalogens rescue neuronal cell death through an activation of AKT and ERK survival signaling. PLoS One 8, e83508.
51. Bazenet C, Lovestone S (2012) Plasma biomarkers for Alzheimer's disease: Much needed but tough to find. Biomark Med 6, 441-454.
52. O'Brien JS, Sampson EL (1965) Lipid composition of the normal human brain: Gray matter, white matter, and myelin. J Lipid Res 6, 537-544.
53. Ginsberg L, Rafique S, Xuereb JH, Rapoport SI, Gershfeld NL (1995) Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer's disease brain. Brain Res 698, 223-226.
54. Han X, Holtzman DM, McKeel DW Jr (2001) Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: Molecular characterization using electrospray ionization mass spectrometry. J Neurochem 77, 1168-1180.
55. Lee J, Culyba EK, Powers ET, Kelly JW (2011) Amyloidbeta forms fibrils by nucleated conformational conversion of oligomers. Nat Chem Biol 7, 602-609.
56. Pike LJ, Han XL, Chung KN, Gross RW (2002) Lipid rafts are enriched in arachidonic acid and plasmenylethanolamine and their composition is independent of caveolin-1 expression: A quantitative electrospray ionization/mass spectrometric analysis. Biochemistry 41, 2075-2088.
57. Munn NJ, Arnio E, Liu D, Zoeller RA, Liscum L (2003) Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport. J Lipid Res 44, 182-192.
58. Liu WW, Todd S, Coulson DTR, Irvine BG, Passmore AP, McGuinness B, McConville M, Craig D, Johnston JA (2009) A novel reciprocal and biphasic relationship between membrane cholesterol andβ-secretase activity in SH-SY5Y cells and in human platelets. J Neurochem 108, 341-349.
59. 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 (2007) Peripheral ethanolamine plasmalogen deficiency: A logical causative factor in Alzheimer's disease and dementia. J Lipid Res 48, 2485-2498.
60. Wood P, Mankidy R, Ritchie S, Heath D, Wood JA, Flax J, Goodenowe DB (2010) Circulating plasmalogen levels and Alzheimer Disease Assessment Scale-Cognitive scores in Alzheimer patients. J Psychiatry Neurosci 35, 59-62.
61. Ifuku M, Katafuchi T, Mawatari S, Noda M, Miake K, Sugiyama M, Fujino T (2012) Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice. J Neuroinflammation 9, 197.
62. Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X, Wenk MR, Goh ELK, Silver DL (2014) Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature 509, 503-506.
63. Han X, Holtzman DM, McKeel DW, Kelley J, Morris JC (2002) Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: Potential role in disease pathogenesis. J Neurochem 82, 809-818.
64. Filippov V, Song MA, Zhang K, Vinters HV, Tung S, Kirsch WM, Yang J, Duerksen-Hughes PJ (2012) Increased ceramide in brains with Alzheimer's and other neurodegenerative diseases. J Alzheimers Dis 29, 537-547.
65. Mielke MM, Bandaru VVR, Haughey NJ, Xia J, Fried LP, Yasar S, Albert M, Varma V, Harris G, Schneider EB, Rabins PV, Bandeen-Roche K, Lyketsos CG, Carlson MC (2012) Serum ceramides increase the risk of Alzheimer disease: The Women's Health and Aging Study II. Neurology 79, 633-641.
66. Mielke MM, Bandaru VV, Haughey NJ, Rabins PV, Lyketsos CG, Carlson MC (2010) Serum sphingomyelins and ceramides are early predictors of memory impairment. Neurobiol Aging 31, 17-24.
67. Han X, Rozen S, Boyle SH, Hellegers C, Cheng H, Burke JR, Welsh-Bohmer KA, Doraiswamy PM, Kaddurah-Daouk R (2011) Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One 6, e21643.
68. Mapstone M, Cheema AK, Fiandaca MS, Zhong X, Mhyre TR, MacArthur LH, Hall WJ, Fisher SG, Peterson DR, Haley JM, Nazar MD, Rich SA, Berlau DJ, Peltz CB, Tan MT, Kawas CH, FederoffHJ (2014) Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med 20, 415-418.
69. de Mello VD, Lankinen M, Schwab U, Kolehmainen M, Lehto S, Seppanen-Laakso T, Oresic M, Pulkkinen L, Uusitupa M, Erkkila AT (2009) Link between plasma ceramides, inflammation and insulin resistance: Association with serum IL-6 concentration in patients with coronary heart disease. Diabetologia 52, 2612-2615.
70. Lyn-Cook LE Jr, Lawton M, Tong M, Silbermann E, Longato L, Jiao P, Mark P, Wands JR, Xu H, de la Monte SM (2009) Hepatic ceramide may mediate brain insulin resistance and neurodegeneration in type 2 diabetes and non-alcoholic steatohepatitis. J Alzheimers Dis 16, 715-729.
71. Tong M, de la Monte SM (2009) Mechanisms of ceramidemediated neurodegeneration. J Alzheimers Dis 16, 705-714.
72. Zhou H, Summers SA, Birnbaum MJ, Pittman RN (1998) Inhibition of Akt kinase by cell-permeable ceramide and its implications for ceramide-induced apoptosis. J Biol Chem 273, 16568-16575.
73. Jolivalt CG, Lee CA, Beiswenger KK, Smith JL, Orlov M, Torrance MA, Masliah E (2008) Defective insulin signaling pathway and increased glycogen synthase kinase-3 activity in the brain of diabetic mice: Parallels with Alzheimer's disease and correction by insulin. J Neurosci Res 86, 3265-3274.
74. Pearce NJ, Arch JR, Clapham JC, Coghlan MP, Corcoran SL, Lister CA, Llano A, Moore GB, Murphy GJ, Smith SA, Taylor CM, Yates JW, Morrison AD, Harper AJ, Roxbee-Cox L, Abuin A, Wargent E, Holder JC (2004) Development of glucose intolerance in male transgenic mice overexpressing human glycogen synthase kinase-3β on a muscle-specific promoter. Metabolism 53, 1322-1330.
75. Hernández F, Gómez de Barreda E, Fuster-Matanzo A, Lucas JJ, Avila J (2010) GSK3: A possible link between beta amyloid peptide and tau protein. Exp Neurol 223, 322-325.
76. da Silva TF, Eira J, Lopes AT, Malheiro AR, Sousa V, Luoma A, Avila RL, Wanders RJ, Just WW, Kirschner DA, Sousa MM, Brites P (2014) Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination. J Clin Invest 124, 2560-2570.
77. Braverman NE, Moser AB (2012) Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta 1822, 1442-1452.
78. Engelmann B (2004) Plasmalogens: Targets for oxidants and major lipophilic antioxidants. Biochem Soc Trans 32, 147-150.
79. Yan Q, Zhang J, Liu H, Babu-Khan S, Vassar R, Biere AL, Citron M, Landreth G (2003) Anti-inflammatory drug therapy alters β-amyloid processing and deposition in an animal model of Alzheimer's disease. J Neurosci 23, 7504-7509.
80. Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW, Hong JT (2008) Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of β-amyloid generation. J Neuroinflammation 5, 37.
81. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 52, 102-110.
82. Tuppo EE, Arias HR (2005) The role of inflammation in Alzheimer's disease. Int J Biochem Cell Biol 37, 289-305.
83. Latorre E, Collado MP, Fernandez I, Aragones MD, Catalan RE (2003) Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis by ceramide. Eur J Biochem 270, 36-46.
84. Coetzee T, Fujita N, Dupree J, Shi R, Blight A, Suzuki K, Suzuki K, Popko B (1996) Myelination in the absence of galactocerebroside and sulfatide: Normal structure with abnormal function and regional instability. Cell 86, 209-219.
85. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein-e type-4 allele and the risk of Alzheimer's disease in lateonset families. Science 261, 921-923.
86. Han X, Cheng H, Fryer JD, Fagan AM, Holtzman DM (2003) Novel role for apolipoprotein E in the central nervous system. Modulation of sulfatide content. J Biol Chem 278, 8043-8051.
87. Fredman P, Mansson JE, Rynmark BM, Josefsen K, Ekblond A, Halldner L, Osterbye T, Horn T, Buschard K (2000) The glycosphingolipid sulfatide in the islets of Langerhans in rat pancreas is processed through recycling: Possible involvement in insulin trafficking. Glycobiology 10, 39-50.
88. Blomqvist M, Osterbye T, Mansson JE, Horn T, Buschard K, Fredman P (2003) Selective lack of the C16:0 fatty acid isoform of sulfatide in pancreas of type II diabetic animal models. APMIS 111, 867-877.
89. Roeske-Nielsen A, Buschard K, Manson J, Rastam L, Lindblad U (2009) A variation in the cerebroside sulfotransferase gene is linked to exercise-modified insulin resistance and to type 2 diabetes. Exp Diabetes Res 2009, 429593.
90. Bovin LF, Fredman P, Mansson JE, Buschard K, Bendtzen K (1999) In vitro production of cytokines is influenced by sulfatide and its precursor galactosylceramide. FEBS Lett 455, 339-343.
91. Andersson K, Buschard K, Fredman P, Kaas A, Lidstrom AM, Madsbad S, Mortensen H, Jan-Eric M (2002) Patients with insulin-dependent diabetes but not those with noninsulin-dependent diabetes have anti-sulfatide antibodies as determined with a new ELISA assay. Autoimmunity 35, 463-468.
92. Llorente A, Skotland T, Sylvänne T, Kauhanen D, Róg T, Orłowski A, Vattulainen I, Ekroos K, Sandvig K (2013) Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim Biophys Acta 1831, 1302-1309.
93. Dinkins MB, Wang G, Bieberich E (2016) Sphingolipidenriched extracellular vesicles and Alzheimer's disease: A decade of research. J Alzheimers Dis, doi: 10.3233/JAD-160567.
94. Théry C, Zitvogel L, Amigorena S (2002) Exosomes: Composition, biogenesis and function. Nat Rev Immunol 2, 569-579.
95. Fiandaca MS, Kapogiannis D, Mapstone M, Boxer A, Eitan E, Schwartz JB, Abner EL, Petersen RC, Federoff HJ, Miller BL, Goetzl EJ (2015) Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A casecontrol study. Alzheimers Dement 11, 600-607.e601.
96. Kapogiannis D, Boxer A, Schwartz JB, Abner EL, Biragyn A, Masharani U, Frassetto L, Petersen RC, Miller BL, Goetzl EJ (2015) Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer's disease. FASEB J 29, 589-596.
97. Phuyal S, Skotland T, Hessvik NP, Simolin H, Øverbye A, Brech A, Parton RG, Ekroos K, Sandvig K, Llorente A (2015) The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells. J Biol Chem 290, 4225-4237.
98. Dinkins MB, Dasgupta S, Wang G, Zhu G, Bieberich E (2014) Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease. Neurobiol Aging 35, 1792-1800.
99. Yuyama K, Sun H, Sakai S, Mitsutake S, Okada M, Tahara H, Furukawa J-i, Fujitani N, Shinohara Y, Igarashi Y (2014) Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J Biol Chem 289, 24488-24498.
100. Martínez-GonzálezMA , de la Fuente-Arrillaga C, Nunez-Cordoba JM, Basterra-Gortari FJ, Beunza JJ, Vazquez Z, Benito S, Tortosa A, Bes-Rastrollo M (2008) Adherence to Mediterranean diet and risk of developing diabetes: Prospective cohort study. BMJ 336, 1348-1351.
101. Kanoski SE, Zhang Y, ZhengW, Davidson TL (2010) The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat. J Alzheimers Dis 21, 207-219.
102. Takechi R, Pallebage-Gamarallage M, Lam V, Giles C, Mamo J (2012) Aging-related changes in blood-brain barrier integrity and the effect of dietary fat. Neurodegener Dis 12, 125-135.
103. BanksWA, Coon AB, Robinson SM, Moinuddin A, Shultz JM, Nakaoke R, Morley JE (2004) Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 53, 1253-1260.
104. Marwarha G, Ghribi O (2012) Leptin signaling and Alzheimer's disease. Am J Neurodegener Dis 1, 245-265.
105. Irie F, Fitzpatrick AL, Lopez OL, Kuller LH, Peila R, Newman AB, Launer LJ (2008) Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE a4: The Cardiovascular Health Study Cognition Study. Arch Neurol 65, 89-93.
106. Notkola I-L, Sulkava R, Pekkanen J, Erkinjuntti T, Ehnholm C, Kivinen P, Tuomilehto J, Nissinen A (1998) Serum total cholesterol, apolipoprotein E e4 allele, and Alzheimer's disease. Neuroepidemiology 17, 14-20.
107. Evans R, Emsley C, Gao S, Sahota A, Hall K, Farlow M, Hendrie H (2000) Serum cholesterol,APOEgenotype, and the risk of Alzheimer's disease: A population-based study of African Americans. Neurology 54, 240-242.