The Potential of ‘Omics to Link Lipid Metabolism and Genetic and Comorbidity Risk Factors of Alzheimer’s Disease in African Americans

  • Kaitlyn E. Stepler
  • Renã A. S. RobinsonEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1118)


Alzheimer’s disease (AD) disproportionately affects African Americans (AAs) and Hispanics, who are more likely to have AD than non-Hispanic Whites (NHWs) and Asian Americans. Racial disparities in AD are multifactorial, with potential contributing factors including genetics, comorbidities, diet and lifestyle, education, healthcare access, and socioeconomic status. Interestingly, comorbidities such as hypertension, type 2 diabetes mellitus, and cardiovascular disease also impact AAs. It is plausible that a common underlying molecular basis to these higher incidences of AD and comorbidities exists especially among AAs. A likely common molecular pathway that is centrally linked to AD and these noted comorbidities is alterations in lipid metabolism. Several genes associated with AD risk—most notably, the ε4 allele of the apolipoprotein E (APOE) gene and several mutations in the ATP-binding cassette transporter A7 (ABCA7) gene—are linked to altered lipid metabolism, especially in AAs. This review explores the role of lipid metabolism in AD broadly, as well as in other comorbidities that are prevalent in AAs. Because there are gaps in our understanding of the molecular basis of higher incidences of AD in AAs, ‘omics approaches such as proteomics and lipidomics are presented as potential methods to improve our knowledge in these areas.


Lipid metabolism Alzheimer’s disease Proteomics African Americans Comorbidities Lipidomics 



The authors acknowledge funding from the Alzheimer’s Association (AARGD-17-533405), Vanderbilt University Start-Up Funds, the University of Pittsburgh Alzheimer Disease Research Center funded by the National Institutes of Health and National Institute on Aging (P50AG005133, RASR), and the Vanderbilt Institute of Chemical Biology (fellowship, KES). We would like to thank Mostafa J. Khan for sharing his lipidomics data.


  1. 1.
    Alzheimer’s Association (2018) 2018 Alzheimer’s disease facts and figures. Alzheimers Dement 14:367–429CrossRefGoogle Scholar
  2. 2.
    Barnes LL, Bennett DA (2014) Alzheimer’s disease in African Americans: risk factors and challenges for the future. Health Aff (Millwood) 33:580–586CrossRefGoogle Scholar
  3. 3.
    Lines L, Sherif NA, Wiener J (2014) Racial and ethnic disparities among individuals with Alzheimer’s disease in the United States: a literature review. RTI Press, Research Triangle Park, NC. Scholar
  4. 4.
    Matthews KA, Xu W, Gaglioti AH, Holt JB, Croft JB, Mack D et al (2018) Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥65 years. Alzheimers Dement. [Epub ahead of print]CrossRefGoogle Scholar
  5. 5.
    Gottesman RF, Fornage M, Knopman DS, Mosley TH (2015) Brain aging in African-Americans: the atherosclerosis risk in communities (ARIC) experience. Curr Alzheimer Res 12:607–613PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Manly JJ, Mayeux R (2004) Ethnic differences in dementia and Alzheimer’s disease. In: Anderson NB, Bulatao RA, Cohen B (eds) Critical perspectives on racial and ethnic differences in health in late life. National Academies Press, Washington, DC. ASIN: B00FBZPHCUGoogle Scholar
  7. 7.
    Mehta KM, Yeo GW (2017) Systematic review of dementia prevalence and incidence in United States race/ethnic populations. Alzheimers Dement 13:72–83PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Alzheimer’s Association (2017) Alzheimer’s disease facts and figures. Alzheimers Dement 13:325–373CrossRefGoogle Scholar
  9. 9.
    Chin AL, Negash S, Hamilton R (2011) Diversity and disparity in dementia: the impact of ethnoracial differences in Alzheimer disease. Alzheimer Dis Assoc Disord 25:187–195PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA (2015) Inequalities in dementia incidence between six racial and ethnic groups over 14 years. Alzheimers Dement 12:216–224CrossRefGoogle Scholar
  11. 11.
    Burke SL, Cadet T, Maddux M (2017) Chronic health illnesses as predictors of mild cognitive impairment among African American older adults. J Natl Med Assoc 110(4):314–325PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Gilligan AM, Malone DC, Warholak TL, Armstrong EP (2012) Racial and ethnic disparities in Alzheimer’s disease pharmacotherapy exposure: an analysis across four state Medicaid populations. Am J Geriatr Pharmacother 10:303–312PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Liu Q, Zhang J (2014) Lipid metabolism in Alzheimer’s disease. Neurosci Bull 30:331–345PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Gamba P, Testa G, Sottero B, Gargiulo S, Poli G, Leonarduzzi G (2012) The link between altered cholesterol metabolism and Alzheimer’s disease. Ann N Y Acad Sci 1259:54–64PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Martins IJ, Berger T, Sharman MJ, Verdile G, Fuller SJ, Martins RN (2009) Cholesterol metabolism and transport in the pathogenesis of Alzheimer’s disease. J Neurochem 111:1275–1308PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    El Gaamouch F, Jing P, Xia J, Cai D (2016) Alzheimer’s disease risk genes and lipid regulators. J Alzheimers Dis 53:15–29PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Burns M, Duff K (2002) Cholesterol in Alzheimer’s disease and tauopathy. Ann N Y Acad Sci 977:367–375PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Sato N, Morishita R (2015) The roles of lipid and glucose metabolism in modulation of β-amyloid, tau, and neurodegeneration in the pathogenesis of Alzheimer disease. Front Aging Neurosci 7:199. Scholar
  19. 19.
    Torres M, Busquets X, Escribá PV (2016) Brain lipids in the pathophysiology and treatment of Alzheimer’s disease. In: Moretti DV (ed) Update on dementia. InTech, Rijeka, pp 127–167. Scholar
  20. 20.
    Wong MW, Braidy N, Poljak A, Pickford R, Thambisetty M, Sachdev PS (2017) Dysregulation of lipids in Alzheimer’s disease and their role as potential biomarkers. Alzheimers Dement 13:810–827PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Zamrini E, Parrish JA, Parsons D, Harrell LE (2004) Medical comorbidity in black and white patients with Alzheimer’s disease. South Med J 97:2–6PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Barnes LL, Leurgans S, Aggarwal NT, Shah RC, Arvanitakis Z, James BD et al (2015) Mixed pathology is more likely in black than white decedents with Alzheimer dementia. Neurology 85:528–534PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Gottesman RF, Schneider AC, Zhou Y, Coresh J, Green E, Gupta N et al (2017) Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA 317:1443–1450PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Wilkins CH, Grant EA, Schmitt SE, McKeel DW, Morris JC (2006) The neuropathology of Alzheimer disease in African American and white individuals. Arch Neurol 63:87–90PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Graff-Radford NR, Besser LM, Crook JE, Kukull WA, Dickson DW (2016) Neuropathological differences by race from the National Alzheimer’s coordinating center. Alzheimers Dement 12:669–677PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Mortimer JA, Graves AB (1993) Education and other socioeconomic determinants of dementia and Alzheimer’s disease. Neurology 43:S39–S44Google Scholar
  27. 27.
    Borenstein AR, Copenhaver CI, Mortimer JA (2006) Early-life risk factors for Alzheimer’s disease. Alzheimer Dis Assoc Disord 20:63–72PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Ramos-Cejudo J, Wisniewski T, Marmar C, Zetterberg H, Blennow K, de Leon MJ et al (2018) Traumatic brain injury and Alzheimer’s disease: the cerebrovascular link. EBioMedicine 28:21–30PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Honig LS, Tang MX, Albert S, Costa R, Luchsinger J, Manly J et al (2003) Stroke and the risk of Alzheimer disease. Arch Neurol 60:1707–1712PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Chakrabarti S, Khemka VK, Banerjee A, Chatterjee G, Ganguly A, Biswas A (2015) Metabolic risk factors of sporadic Alzheimer’s disease: implications in the pathology, pathogenesis and treatment. Aging Dis 6:282–299PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Matsuzaki T, Sasaki K, Hata J, Hirakawa Y, Fujimi K, Ninomiya T et al (2011) Association of Alzheimer disease pathology with abnormal lipid metabolism: the Hisayama study. Neurology 77:1068–1075PubMedCrossRefGoogle Scholar
  32. 32.
    Nday CM, Eleftheriadou D, Jackson G (2017) Shared pathological pathways of Alzheimer’s disease with specific comorbidities: current perspectives and interventions. J Neurochem 144(4):360–389CrossRefGoogle Scholar
  33. 33.
    Carnethon MR, Pu J, Howard G, Albert MA, Anderson CAM, Bertoni AG et al (2017) Cardiovascular health in African Americans: a scientific statement from the American Heart Association. Circulation 136:e393–e423PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Di Paolo G, Kim TW (2011) Linking lipids to Alzheimer’s disease: cholesterol and beyond. Nat Rev Neurosci 12:284–296PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Martins IJ (2015) Diabetes and cholesterol dyshomeostasis involve abnormal α-synuclein and amyloid beta transport in neurodegenerative diseases. Austin Alzheimer’s and Parkinson’s Disease.
  36. 36.
    Evans RM, Emsley CL, Gao S, Sahota A, Hall KS, Farlow MR et al (2000) Serum cholesterol, APOE genotype, and the risk of Alzheimer’s disease: a population-based study of African Americans. Neurology 54:240–242PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Xu W, Tan L, Wang H-F, Jiang T, Tan M-S, Tan L et al (2015) Meta-analysis of modifiable risk factors for Alzheimer’s disease. J Neurol Neurosurg Psychiatry 86(12):1299–1306PubMedPubMedCentralGoogle Scholar
  38. 38.
    Gonzalez HM, Tarraf W, Harrison K, Windham BG, Tingle J, Alonso A et al (2017) Midlife cardiovascular health and 20-year cognitive decline: atherosclerosis risk in communities study results. Alzheimers Dement 14(5):579–589PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Howard G, Safford MM, Moy CS, Howard VJ, Kleindorfer DO, Unverzagt FW et al (2017) Racial differences in the incidence of cardiovascular risk factors in older black and white adults. J Am Geriatr Soc 65:83–90PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Osuji CU, Omejua EG, Onwubuya EI, Ahaneku GI (2012) Serum lipid profile of newly diagnosed hypertensive patients in Nnewi, south-East Nigeria. Int J Hypertens 2012:710486. Scholar
  41. 41.
    Barnes DE, Yaffe K (2011) The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 10:819–828PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Arvanitakis Z, Capuano AW, Lamar M, Shah RC, Barnes LL, Bennett DA et al (2018) Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology 91(6):e517–e525PubMedCrossRefGoogle Scholar
  43. 43.
    Williamson JW (2018) A randomized trial of intensive versus standard systolic blood pressure control and the risk of mild cognitive impairment and dementia: results from SPRINT MIND. Proceedings of Alzheimer’s Association International Conference 2018, Chicago, IL, USA. ID 27525Google Scholar
  44. 44.
    Nasrallah IM (2018) A randomized trial of intensive versus standard systolic blood pressure control on brain structure: results from SPRINT MIND MRI. Proceedings of Alzheimer’s Association International Conference 2018, Chicago, IL, USA. ID 27526Google Scholar
  45. 45.
    Fuchs FD (2011) Why do black Americans have higher prevalence of hypertension? An enigma still unsolved. Hypertension 57:379–380PubMedCrossRefGoogle Scholar
  46. 46.
    Lackland DT (2014) Racial differences in hypertension: implications for high blood pressure management. Am J Med Sci 348:135–138PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Muntner P, He J, Cutler JA, Wildman RP, Whelton PK (2004) Trends in blood pressure among children and adolescents. JAMA 291:2107–2113PubMedCrossRefGoogle Scholar
  48. 48.
    Redmond N, Baer HJ, Hicks LS (2011) Health behaviors and racial disparity in blood pressure control in the National Health and nutrition examination survey. Hypertension 57:383–389PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Arnold SE, Arvanitakis Z, Macauley-Rambach SL, Koenig AM, Wang HY, Ahima RS et al (2018) Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol 14(3):168–181PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Boden G, Laakso M (2004) Lipids and glucose in type 2 diabetes: what is the cause and effect? Diabetes Care 27:2253–2259PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Savage DB, Petersen KF, Shulman GI (2007) Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 87:507–520PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Schilling MA (2016) Unraveling Alzheimer’s: making sense of the relationship between diabetes and Alzheimer’s disease. J Alzheimers Dis 51:961–977PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Marseglia A, Fratiglioni L, Kalpouzos G, Wang R, Bäckman L, Xu W (2018) Prediabetes and diabetes accelerate cognitive decline and predict microvascular lesions: a population-based cohort study. Alzheimers Dement Aug 13. doi: 10.1016/j.jalz.2018.06.3060. [Epub ahead of print]CrossRefGoogle Scholar
  54. 54.
    Cheng D, Noble J, Tang MX, Schupf N, Mayeux R, Luchsinger JA (2011) Type 2 diabetes and late-onset Alzheimer’s disease. Dement Geriatr Cogn Disord 31:424–430PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Bangen KJ, Gu Y, Gross AL, Schneider BC, Skinner JC, Benitez A et al (2015) Relationship between type 2 diabetes mellitus and cognitive change in a multiethnic elderly cohort. J Am Geriatr Soc 63:1075–1083PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Willette AA, Johnson SC, Birdsill AC, Sager MA, Christian B, Baker LD et al (2015) Insulin resistance predicts brain amyloid deposition in late middle-aged adults. Alzheimers Dement 11:504–510.e1PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Pimentel dos Santos Matioli MN, Suemoto CK, Rodriguez RD, Farias DS, da Silva MM, Paraizo Leite RE et al (2017) Diabetes is not associated with Alzheimer’s disease neuropathology. J Alzheimers Dis 60:1035–1043CrossRefGoogle Scholar
  58. 58.
    Heitner J, Dickson D (1997) Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects: a retrospective postmortem immunocytochemical and histofluorescent study. Neurology 49:1306–1311PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Arvanitakis Z, Schneider JA, Wilson RS, Li Y, Arnold SE, Wang Z et al (2006) Diabetes is related to cerebral infarction but not to AD pathology in older persons. Neurology 67:1960–1965PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Abner EL, Nelson PT, Kryscio RJ, Schmitt FA, Fardo DW, Woltjer RL et al (2016) Diabetes is associated with cerebrovascular but not Alzheimer’s disease neuropathology. Alzheimers Dement 12:882–889PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad B et al (2010) Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 75:1195–1202PubMedCrossRefGoogle Scholar
  62. 62.
    Brancati FL, Kao W, Folsom AR, Watson RL, Szklo M (2000) Incident type 2 diabetes mellitus in African American and white adults: the atherosclerosis risk in communities study. JAMA 283:2253–2259PubMedCrossRefGoogle Scholar
  63. 63.
    Marshall M (2005) Diabetes in African Americans. Postgrad Med J 81:734–740PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Mayeda ER, Haan MN, Neuhaus J, Yaffe K, Knopman DS, Sharrett AR et al (2014) Type 2 diabetes and cognitive decline over 14 years in middle-aged African Americans and whites: the ARIC brain MRI study. Neuroepidemiology 43:220–227PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Arvanitakis Z, Bennett DA, Wilson RS, Barnes LL (2010) Diabetes and cognitive systems in older black and white persons. Alzheimer Dis Assoc Disord 24:37–42PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Hendrie HC, Zheng M, Lane KA, Ambuehl R, Purnell C, Li S et al (2018) Changes of glucose levels precede dementia in African-Americans with diabetes but not in Caucasians. Alzheimers Dement 14(12):1572-1579CrossRefGoogle Scholar
  67. 67.
    Hendrie HC, Zheng M, Li W, Lane K, Ambuehl R, Purnell C et al (2017) Glucose level decline precedes dementia in elderly African Americans with diabetes. Alzheimers Dement 13:111–118PubMedCrossRefGoogle Scholar
  68. 68.
    Azarpazhooh MR, Avan A, Cipriano LE, Munoz DG, Sposato LA, Hachinski V (2017) Concomitant vascular and neurodegenerative pathologies double the risk of dementia. Alzheimers Dement 14:148–156PubMedCrossRefGoogle Scholar
  69. 69.
    Jefferson AL, Hohman TJ, Liu D, Haj-Hassan S, Gifford KA, Benson EM et al (2015) Adverse vascular risk is related to cognitive decline in older adults. J Alzheimers Dis 44:1361–1373PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Li J, Wang YJ, Zhang M, Xu ZQ, Gao CY, Fang CQ et al (2011) Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease. Neurology 76:1485–1491PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M et al (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s coordinating Centre. Brain 136:2697–2706PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Gorelick PB (1998) Cerebrovascular disease in African Americans. Stroke 29:2656–2664PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Morgenstern LB, Spears WD, Goff DC, Grotta JC, Nichaman MZ (1997) African Americans and women have the highest stroke mortality in Texas. Stroke 28:15–18PubMedCrossRefGoogle Scholar
  74. 74.
    Sandberg G, Stewart W, Smialek J, Troncoso JC (2001) The prevalence of the neuropathological lesions of Alzheimer’s disease is independent of race and gender. Neurobiol Aging 22:169–175PubMedCrossRefGoogle Scholar
  75. 75.
    Arvanitakis Z, Leurgans SE, Fleischman DA, Schneider JA, Rajan KB, Pruzin JJ et al (2018) Memory complaints, dementia, and neuropathology in older blacks and whites. Ann Neurol 83:718–729PubMedCrossRefGoogle Scholar
  76. 76.
    Raj T, Chibnik LB, McCabe C, Wong A, Replogle JM, Yu L et al (2017) Genetic architecture of age-related cognitive decline in African Americans. Neurol Genet 3(1):e125. Scholar
  77. 77.
    Vrièze FW-D, Compton D, Womick M, Arepalli S, Adighibe O, Li L et al (2007) ABCA1 polymorphisms and Alzheimer’s disease. Neurosci Lett 416:180–183PubMedCentralCrossRefPubMedGoogle Scholar
  78. 78.
    Koldamova R, Fitz NF, Lefterov I (2010) The role of ATP-binding cassette transporter A1 in Alzheimer’s disease and neurodegeneration. Biochim Biophys Acta 1801:824–830PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Fehér Á, Giricz Z, Juhász A, Pákáski M, Janka Z, Kálmán J (2018) ABCA1 rs2230805 and rs2230806 common gene variants are associated with Alzheimer’s disease. Neurosci Lett 664:79–83PubMedCrossRefGoogle Scholar
  80. 80.
    Aikawa T, Holm ML, Kanekiyo T (2018) ABCA7 and pathogenic pathways of Alzheimer’s disease. Brain Sci 8(2):E27. Scholar
  81. 81.
    Almeida JFF, Dos Santos LR, Trancozo M, de Paula F (2018) Updated meta-analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 variants in Alzheimer’s disease. J Mol Neurosci 64(3):471–477PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM et al (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 43:429–435PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J et al (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 43:436–441PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Cuyvers E, De Roeck A, Van den Bossche T, Van Cauwenberghe C, Bettens K, Vermeulen S et al (2015) Mutations in ABCA7 in a Belgian cohort of Alzheimer’s disease patients: a targeted resequencing study. Lancet Neurol 14:814–822PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C et al (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 45:1452–1458PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Zhou Q, Zhao F, Lv Z-P, Zheng C-G, Zheng W-D, Sun L et al (2014) Association between APOC1 polymorphism and Alzheimer’s disease: a case-control study and meta-analysis. PLoS One 9(1):e87017. Scholar
  87. 87.
    Petit-Turcotte C, Stohl SM, Beffert U, Cohn JS, Aumont N, Tremblay M et al (2001) Apolipoprotein C-I expression in the brain in Alzheimer’s disease. Neurobiol Dis 8:953–963PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Ki C-S, Na DL, Kim DK, Kim HJ, Kim J-W (2002) Genetic association of an apolipoprotein C-I (APOC1) gene polymorphism with late-onset Alzheimer’s disease. Neurosci Lett 319:75–78PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Desai PP, Hendrie HC, Evans RM, Murrell JR, DeKosky ST, Kamboh MI (2003) Genetic variation in apolipoprotein D affects the risk of Alzheimer disease in African-Americans. Am J Med Genet B Neuropsychiatr Genet 116B:98–101PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Zhao N, Liu C-C, Qiao W, Bu G (2017) Apolipoprotein E, receptors, and modulation of Alzheimer’s disease. Biol Psychiatry 83(4):347–357PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Reitz C, Jun G, Naj A, Rajbhandary R, Vardarajan BN, Wang L-S et al (2013) Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ε4, and the risk of late-onset Alzheimer disease in African Americans. JAMA 309:1483–1492PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Reitz C, Mayeux R (2014) Genetics of Alzheimer’s disease in Caribbean Hispanic and African American populations. Biol Psychiatry 75:534–541PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Seshadri S, Fitzpatrick AL, Ikram MA, DeStefano AL, Gudnason V, Boada M et al (2010) Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303:1832–1840PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Bertram L, Lange C, Mullin K, Parkinson M, Hsiao M, Hogan MF et al (2008) Genome-wide association analysis reveals putative Alzheimer’s disease susceptibility loci in addition to APOE. Am J Hum Genet 83:623–632PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Lambert J-C, Heath S, Even G, Campion D, Sleegers K, Hiltunen M et al (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet 41:1094–1099CrossRefGoogle Scholar
  96. 96.
    Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML et al (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41:1088–1093PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F et al (2007) The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer’s disease. Nat Genet 39:168–177PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Lee JH, Cheng R, Schupf N, Manly J, Lantigua R, Stern Y et al (2007) The association between genetic variants in SORL1 and Alzheimer’s disease in an urban, multiethnic, community-based cohort. Arch Neurol 64:501–506PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Chou C-T, Liao Y-C, Lee W-J, Wang S-J, Fuh J-L (2016) SORL1 gene, plasma biomarkers, and the risk of Alzheimer’s disease for the Han Chinese population in Taiwan. Alzheimers Res Ther 8(1):53. Scholar
  100. 100.
    Ghani M, Reitz C, Cheng R, Vardarajan BN, Jun G, Sato C et al (2015) Association of long runs of homozygosity with Alzheimer disease among African American individuals. JAMA Neurol 72:1313–1323PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Picard C, Julien C, Frappier J, Miron J, Théroux L, Dea D et al (2018) Alterations in cholesterol metabolism-related genes in sporadic Alzheimer’s disease. Neurobiol Aging 66:180.e1–180.e9. Scholar
  102. 102.
    Bales KR (2010) Brain lipid metabolism, apolipoprotein E and the pathophysiology of Alzheimer’s disease. Neuropharmacology 59:295–302PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Girard H, Potvin O, Nugent S, Dallaire-Theroux C, Cunnane S, Duchesne S (2017) Faster progression from MCI to probable AD for carriers of a single-nucleotide polymorphism associated with type 2 diabetes. Neurobiol Aging 64:157.e11–157.e17. Scholar
  104. 104.
    Pirttila T, Soininen H, Heinonen O, Lehtimaki T, Bogdanovic N, Paljarvi L et al (1996) Apolipoprotein E (apoE) levels in brains from Alzheimer disease patients and controls. Brain Res 722:71–77PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Peila R, Rodriguez BL, Launer LJ (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia aging study. Diabetes 51:1256–1262CrossRefGoogle Scholar
  106. 106.
    Corlier F, Hafzalla G, Faskowitz J, Kuller LH, Becker JT, Lopez OL et al (2018) Systemic inflammation as a predictor of brain aging: contributions of physical activity, metabolic risk, and genetic risk. NeuroImage 172:118–129PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Hall K, Murrell J, Ogunniyi A, Deeg M, Baiyewu O, Gao S et al (2006) Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba. Neurology 66:223–227PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Lin Y-F, Smith AV, Aspelund T, Betensky RA, Smoller JW, Gudnason V et al (2018) Genetic overlap between vascular pathologies and Alzheimer’s dementia and potential causal mechanisms. Alzheimers Dement Sep 19. doi: 10.1016/j.jalz.2018.08.002. [Epub ahead of print]CrossRefGoogle Scholar
  109. 109.
    Cukier HN, Kunkle BW, Vardarajan BN, Rolati S, Hamilton-Nelson KL, Kohli MA et al (2016) ABCA7 frameshift deletion associated with Alzheimer disease in African Americans. Neurol Genet 2(3):e79. Scholar
  110. 110.
    Vasquez JB, Fardo DW, Estus S (2013) ABCA7 expression is associated with Alzheimer’s disease polymorphism and disease status. Neurosci Lett 556:58–62PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Hohman TJ, Cooke-Bailey JN, Reitz C, Jun G, Naj A, Beecham GW et al (2016) Global and local ancestry in African-Americans: implications for Alzheimer’s disease risk. Alzheimers Dement 12:233–243PubMedCrossRefGoogle Scholar
  112. 112.
    Reitz C, Mayeux R (2014) Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol 88:640–651PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Han Z, Huang H, Gao Y, Huang Q (2017) Functional annotation of Alzheimer’s disease associated loci revealed by GWASs. PLoS One 12(6):e0179677. Scholar
  114. 114.
    Jones L, Harold D, Williams J (2010) Genetic evidence for the involvement of lipid metabolism in Alzheimer’s disease. Biochim Biophys Acta 1801:754–761PubMedCrossRefGoogle Scholar
  115. 115.
    Fitz NF, Cronican AA, Saleem M, Fauq AH, Chapman R, Lefterov I et al (2012) Abca1 deficiency affects Alzheimer’s disease-like phenotype in human ApoE4 but not in ApoE3-targeted replacement mice. J Neurosci 32:13125–13136PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Wahrle SE, Jiang H, Parsadanian M, Kim J, Li A, Knoten A et al (2008) Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest 118:671–682PubMedPubMedCentralGoogle Scholar
  117. 117.
    Felsky D, Szeszko P, Yu L, Honer WG, De Jager PL, Schneider JA et al (2013) The SORL1 gene and convergent neural risk for Alzheimer’s disease across the human lifespan. Mol Psychiatry 19:1125–1132PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Power MC, Rawlings A, Sharrett AR, Bandeen-Roche K, Coresh J, Ballantyne CM et al (2017) Association of midlife lipids with 20-year cognitive change: a cohort study. Alzheimers Dement 14(2):167–177PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Koch M, DeKosky ST, Fitzpatrick AL, Furtado JD, Lopez OL, Kuller LH et al (2018) Apolipoproteins and Alzheimer’s pathophysiology. Alzheimer’s Dement (Amst) 10:545. Scholar
  120. 120.
    Hughes TM, Lopez OL, Evans RW, Kamboh MI, Williamson JD, Klunk WE et al (2014) Markers of cholesterol transport are associated with amyloid deposition in the brain. Neurobiol Aging 35:802–807PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Chiasserini D, Biscetti L, Eusebi P, Salvadori N, Frattini G, Simoni S et al (2017) Differential role of CSF fatty acid binding protein 3, α-synuclein, and Alzheimer’s disease core biomarkers in Lewy body disorders and Alzheimer’s dementia. Alzheimers Res Ther 9(1):52. Scholar
  122. 122.
    Krishnan B, Kayed R, Taglialatela G (2018) Elevated phospholipase D isoform 1 in Alzheimer’s disease patients’ hippocampus: relevance to synaptic dysfunction and memory deficits. Alzheimers Dement (N.Y.) 4:89–102Google Scholar
  123. 123.
    Ferguson SA, Panos JJ, Sloper D, Varma V (2017) Neurodegenerative markers are increased in postmortem BA21 tissue from African Americans with Alzheimer’s disease. J Alzheimers Dis 59:57–66PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Moya-Alvarado G, Gershoni-Emek N, Perlson E, Bronfman FC (2015) Neurodegeneration and Alzheimer’s disease. What can proteomics tell us about the Alzheimer’s brain? Mol Cell Proteomics 15(2):409–425PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Robinson RAS, Amin B, Guest PC (2017) Multiplexing biomarker methods, proteomics and considerations for Alzheimer’s disease. Adv Exp Med Biol 974:21–48PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Andreev VP, Petyuk VA, Brewer HM, Karpievitch YV, Xie F, Clarke J et al (2012) Label-free quantitative LC-MS proteomics of Alzheimer’s disease and normally aged human brains. J Proteome Res 11:3053–3067PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Begcevic I, Kosanam H, Martinez-Morillo E, Dimitromanolakis A, Diamandis P, Kuzmanov U et al (2013) Semiquantitative proteomic analysis of human hippocampal tissues from Alzheimer’s disease and age-matched control brains. Clin Proteomics 10(1):5. Scholar
  128. 128.
    Evans AR, Gu L, Guerrero R, Robinson RAS (2015) Global cPILOT analysis of the APP/PS-1 mouse liver proteome. Proteomics Clin Appl 9:872–884PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Fania C, Arosio B, Capitanio D, Torretta E, Gussago C, Ferri E et al (2017) Protein signature in cerebrospinal fluid and serum of Alzheimer’s disease patients: the case of apolipoprotein A-1 proteoforms. PLoS One 12(6):e0179280. Scholar
  130. 130.
    Hondius DC, van Nierop P, Li KW, Hoozemans JJM, van der Schors RC, van Haastert ES et al (2016) Profiling the human hippocampal proteome at all pathologic stages of Alzheimer’s disease. Alzheimers Dement 12:654–668PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Lopez MF, Mikulskis A, Kuzdzal S, Bennett DA, Kelly J, Golenko E et al (2005) High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein–bound mass signatures. Clin Chem 51:1946–1954PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Manavalan A, Mishra M, Feng L, Sze SK, Akatsu H, Heese K (2013) Brain site-specific proteome changes in aging-related dementia. Exp Mol Med 45:e39. Scholar
  133. 133.
    Minjarez B, Calderon-Gonzalez KG, Rustarazo ML, Herrera-Aguirre ME, Labra-Barrios ML, Rincon-Limas DE et al (2016) Identification of proteins that are differentially expressed in brains with Alzheimer’s disease using iTRAQ labeling and tandem mass spectrometry. J Proteome 139:103–121CrossRefGoogle Scholar
  134. 134.
    Muenchhoff J, Poljak A, Song F, Raftery M, Brodaty H, Duncan M et al (2015) Plasma protein profiling of mild cognitive impairment and Alzheimer’s disease across two independent cohorts. J Alzheimers Dis 43:1355–1373PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Musunuri S, Wetterhall M, Ingelsson M, Lannfelt L, Artemenko K, Bergquist J et al (2014) Quantification of the brain proteome in Alzheimer’s disease using multiplexed mass spectrometry. J Proteome Res 13:2056–2068PubMedCrossRefPubMedCentralGoogle Scholar
  136. 136.
    Neuner SM, Wilmott LA, Hoffmann BR, Mozhui K, Kaczorowski CC (2017) Hippocampal proteomics defines pathways associated with memory decline and resilience in normal aging and Alzheimer’s disease mouse models. Behav Brain Res 322:288–298PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Sultana R, Boyd-Kimball D, Cai J, Pierce WM, Klein JB, Merchant M et al (2007) Proteomics analysis of the Alzheimer’s disease hippocampal proteome. J Alzheimers Dis 11:153–164PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Tsuji T, Shiozaki A, Kohno R, Yoshizato K, Shimohama S (2002) Proteomic profiling and neurodegeneration in Alzheimer’s disease. Neurochem Res 27:1245–1253PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Zahid S, Oellerich M, Asif AR, Ahmed N (2014) Differential expression of proteins in brain regions of Alzheimer’s disease patients. Neurochem Res 39:208–215PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Gu L, Evans AR, Robinson RAS (2015) Sample multiplexing with cysteine-selective approaches: cysDML and cPILOT. J Am Soc Mass Spectrom 26:615–630PubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    Aluise CD, Robinson RAS, Beckett TL, Murphy MP, Cai J, Pierce WM et al (2010) Preclinical Alzheimer disease: brain oxidative stress, Aβ peptide & proteomics. Neurobiol Dis 39:221–228PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Aluise CD, Robinson RAS, Cai J, Pierce WM, Markesbery WR, Butterfield DA (2011) Redox proteomics analyses of brains from subjects with amnestic mild cognitive impairment compared to brains from subjects with preclinical Alzheimer’s disease: insights into memory loss in MCI. J Alzheimers Dis 23:257–269PubMedCrossRefGoogle Scholar
  143. 143.
    Castegna A, Aksenov M, Thongboonkerd V, Klein JB, Pierce WM, Booze R et al (2002) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part II: Dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem 82:1524–1532PubMedCrossRefGoogle Scholar
  144. 144.
    Reed TT, Pierce WM Jr, Turner DM, Markesbery WR, Butterfield DA (2009) Proteomic identification of nitrated brain proteins in early Alzheimer’s disease inferior parietal lobule. J Cell Mol Med 13:2019–2029PubMedCrossRefGoogle Scholar
  145. 145.
    Robinson RAS, Joshi G, Huang Q, Sultana R, Baker AS, Cai J et al (2011) Proteomics analysis of brain proteins in APP/PS-1 human double mutant knock-in mice with increasing amyloid β-peptide deposition: insights into the effects of in vivo treatment with N-acetylcysteine as a potential therapeutic intervention in mild cognitive impairment and Alzheimer disease. Proteomics 11:4243–4256PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Ping L, Duong DM, Yin L, Gearing M, Lah JJ, Levey AI et al (2018) Global quantitative analysis of the human brain proteome in Alzheimer’s and Parkinson’s disease. Sci Data 5:180036. Scholar
  147. 147.
    Brinkmalm A, Portelius E, Ohrfelt A, Brinkmalm G, Andreasson U, Gobom J et al (2015) Explorative and targeted neuroproteomics in Alzheimer’s disease. Biochim Biophys Acta 1854:769–778PubMedCrossRefGoogle Scholar
  148. 148.
    Korolainen MA, Nyman TA, Aittokallio T, Pirttila T (2010) An update on clinical proteomics in Alzheimer’s research. J Neurochem 112:1386–1414PubMedCrossRefGoogle Scholar
  149. 149.
    Papassotiropoulos A, Fountoulakis M, Dunckley T, Stephan DA, Reiman EM (2006) Genetics, transcriptomics, and proteomics of Alzheimer’s disease. J Clin Psychiatry 67:652–670PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Paterson RW, Heywood WE, Heslegrave AJ, Magdalinou NK, Andreasson U, Sirka E et al (2016) A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer’s disease pathology. Transl Psychiatry 6(11):e952. Scholar
  151. 151.
    Heywood WE, Galimberti D, Bliss E, Sirka E, Paterson RW, Magdalinou NK et al (2015) Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay. Mol Neurodegener 10:64. Scholar
  152. 152.
    Begcevic I, Brinc D, Brown M, Martinez-Morillo E, Goldhardt O, Grimmer T et al (2018) Brain-related proteins as potential CSF biomarkers of Alzheimer’s disease: a targeted mass spectrometry approach. J Proteome 182:12–20CrossRefGoogle Scholar
  153. 153.
    Yu L, Petyuk VA, Gaiteri C, Mostafavi S, Young-Pearse T, Shah RC et al (2018) Targeted brain proteomics uncover multiple pathways to Alzheimer’s dementia. Ann Neurol 84(1):78–88PubMedCrossRefGoogle Scholar
  154. 154.
    Brinkmalm G, Sjödin S, Simonsen AH, Hasselbalch SG, Zetterberg H, Brinkmalm A et al (2018) A parallel reaction monitoring mass spectrometric method for analysis of potential CSF biomarkers for Alzheimer’s disease. Proteomics Clin Appl 12(1). Scholar
  155. 155.
    Chang RY, Etheridge N, Dodd PR, Nouwens AS (2014) Targeted quantitative analysis of synaptic proteins in Alzheimer’s disease brain. Neurochem Int 75:66–75PubMedCrossRefGoogle Scholar
  156. 156.
    Oeckl P, Metzger F, Nagl M, von Arnim CA, Halbgebauer S, Steinacker P et al (2016) Alpha-, beta-, and gamma-synuclein quantification in cerebrospinal fluid by multiple reaction monitoring reveals increased concentrations in Alzheimer’s and Creutzfeldt-Jakob disease but no alteration in synucleinopathies. Mol Cell Proteomics 15:3126–3138PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Dittrich J, Adam M, Maas H, Hecht M, Reinicke M, Ruhaak LR et al (2018) Targeted on-line SPE-LC-MS/MS assay for the quantitation of 12 apolipoproteins from human blood. Proteomics 18(3–4). Scholar
  158. 158.
    Chen J, Wang M, Turko IV (2012) Mass spectrometry quantification of clusterin in the human brain. Mol Neurodegener 7:41. Scholar
  159. 159.
    Henderson CM, Bollinger JG, Becker JO, Wallace JM, Laha TJ, MacCoss MJ et al (2017) Quantification by nano liquid chromatography parallel reaction monitoring mass spectrometry of human apolipoprotein A-I, apolipoprotein B, and hemoglobin A1c in dried blood spots. Proteomics Clin Appl 11(7–8). Scholar
  160. 160.
    Cheon MS, Kim SH, Fountoulakis M, Lubec G (2003) Heart type fatty acid binding protein (H-FABP) is decreased in brains of patients with down syndrome and Alzheimer’s disease. J Neural Transm Suppl 67:225–234CrossRefGoogle Scholar
  161. 161.
    Ijsselstijn L, Papma JM, Dekker LJ, Calame W, Stingl C, Koudstaal PJ et al (2013) Serum proteomics in amnestic mild cognitive impairment. Proteomics 13:2526–2533PubMedCrossRefPubMedCentralGoogle Scholar
  162. 162.
    Kennedy MA, Moffat TC, Gable K, Ganesan S, Niewola-Staszkowska K, Johnston A et al (2016) A signaling lipid associated with Alzheimer’s disease promotes mitochondrial dysfunction. Sci Rep 6:19332. Scholar
  163. 163.
    Li D, Misialek JR, Boerwinkle E, Gottesman RF, Sharrett AR, Mosley TH et al (2017) Prospective associations of plasma phospholipids and mild cognitive impairment/dementia among African Americans in the ARIC neurocognitive study. Alzheimers Dement (Amst) 6:1–10Google Scholar
  164. 164.
    Hasin Y, Seldin M, Lusis A (2017) Multi-omics approaches to disease. Genome Biol 18(1):83. Scholar
  165. 165.
    Karahalil B (2016) Overview of systems biology and omics technologies. Curr Med Chem 23:4221–4230PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Pimplikar SW (2017) Multi-omics and Alzheimer’s disease: a slower but surer path to an efficacious therapy? Am J Physiol Cell Physiol 313:C1–C2PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    Tosto G, Reitz C (2016) Use of “omics” technologies to dissect neurologic disease. Handb Clin Neurol 138:91–106PubMedCrossRefPubMedCentralGoogle Scholar
  168. 168.
    Jaeger PA, Lucin KM, Britschgi M, Vardarajan B, Huang R-P, Kirby ED et al (2016) Network-driven plasma proteomics expose molecular changes in the Alzheimer’s brain. Mol Neurodegener 11:31. Scholar
  169. 169.
    Seyfried NT, Dammer EB, Swarup V, Nandakumar D, Duong DM, Yin L et al (2017) A multi-network approach identifies protein-specific co-expression in asymptomatic and symptomatic Alzheimer’s disease. Cell Syst 4:60–72.e4PubMedCrossRefGoogle Scholar
  170. 170.
    Zhang Q, Ma C, Gearing M, Wang PG, Chin LS, Li L (2018) Integrated proteomics and network analysis identifies protein hubs and network alterations in Alzheimer’s disease. Acta Neuropathol Commun 6(1):19. Scholar
  171. 171.
    Whiley L, Sen A, Heaton J, Proitsi P, García-Gómez D, Leung R et al (2014) Evidence of altered phosphatidylcholine metabolism in Alzheimer’s disease. Neurobiol Aging 35:271–278PubMedCrossRefGoogle Scholar
  172. 172.
    Klavins K, Koal T, Dallmann G, Marksteiner J, Kemmler G, Humpel C (2015) The ratio of phosphatidylcholines to lysophosphatidylcholines in plasma differentiates healthy controls from patients with Alzheimer’s disease and mild cognitive impairment. Alzheimers Dement (Amst) 1:295–302Google Scholar
  173. 173.
    Li D, Misialek JR, Boerwinkle E, Gottesman RF, Sharrett AR, Mosley TH et al (2016) Plasma phospholipids and prevalence of mild cognitive impairment and/or dementia in the ARIC neurocognitive study (ARIC-NCS). Alzheimers Dement (Amst) 3:73–82Google Scholar
  174. 174.
    Mielke MM, Bandaru VVR, Haughey NJ, Rabins PV, Lyketsos CG, Carlson MC (2010) Serum sphingomyelins and ceramides are early predictors of memory impairment. Neurobiol Aging 31:17–24PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of ChemistryVanderbilt UniversityNashvilleUSA
  2. 2.Vanderbilt Memory and Alzheimer’s CenterVanderbilt University Medical CenterNashvilleUSA
  3. 3.Vanderbilt Institute of Chemical BiologyVanderbilt UniversityNashvilleUSA

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