Bacteroidetes Neurotoxins and Inflammatory Neurodegeneration

  • Yuhai Zhao
  • Walter J. Lukiw


The gram-negative facultative anaerobe Bacteroides fragilis (B. fragilis) constitutes an appreciable proportion of the human gastrointestinal (GI)-tract microbiome. As is typical of most gram-negative bacilli, B. fragilis secretes an unusually complex mixture of neurotoxins including the extremely pro-inflammatory lipopolysaccharide BF-LPS. LPS (i) has recently been shown to associate with the periphery of neuronal nuclei in sporadic Alzheimer’s disease (AD) brain and (ii) promotes the generation of the inflammatory transcription factor NF-kB (p50/p65 complex) in human neuronal-glial cells in primary-culture. In turn, the NF-kB (p50/p65 complex) strongly induces the transcription of a small family of pro-inflammatory microRNAs (miRNAs) including miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, and miRNA-155. These ultimately bind with the 3′-untranslated region (3′-UTR) of several target messenger RNAs (mRNAs) and thereby reduce their expression. Down-regulated mRNAs include those encoding complement factor-H (CFH), an SH3-proline-rich multi-domain-scaffolding protein of the postsynaptic density (SHANK3), and the triggering receptor expressed in myeloid/microglial cells (TREM2), as is observed in sporadic AD brain. Hence, a LPS normally confined to the GI tract is capable of driving a NF-kB-miRNA-mediated deficiency in gene expression that contributes to alterations in synaptic-architecture and synaptic-deficits, amyloidogenesis, innate-immune defects, and progressive inflammatory signaling, all of which are characteristics of AD-type neurodegeneration. This article will review the most recent research which supports the idea that bacterial components of the GI tract microbiome such as BF-LPS can transverse biophysical barriers and contribute to AD-type change. For the first-time, these results indicate that specific GI tract microbiome-derived neurotoxins have a strong pathogenic role in eliciting alterations in NF-kB-miRNA-directed gene expression that drives the AD process.


Alzheimer’s disease Amyloidogenesis Bacteroides fragilis Lipopolysaccharide Messenger RNA microRNA Microbiome Neuroinflammation Phagocytosis Synaptogenesis 



Alzheimer’s disease

B. fragilis

Bacteroides fragilis




Bacteroides fragilis lipopolysaccharide


Messenger RNA





This work was presented in part at the Vavilov Institute of General Genetics (VIGG) Autumn Seminar Series (Институт общей генетики имени Вавилова Осень 2017 Семинар серии) in Moscow, Russia, October 2017, at the Society for Neuroscience (SFN) 47th Annual Meeting November 2017 in Washington DC, USA. Sincere thanks are extended to Drs. F Culicchia, C Eicken, C Hebel, and W Poon for short post-mortem interval (PMI) human brain tissues or extracts, DNA and miRNA array work, and initial data interpretation, and to AI Pogue, D Guillot, Lin Cong, and J Lockwood for expert technical assistance. Additional thanks are extended to the many physicians and neuropathologists of Canada, the USA, and Russia who have provided high-quality and short post-mortem interval human brain and retinal tissues and GI tract extracts for scientific study. Additional human control and AD brain tissues were provided by the Memory Impairments and Neurological Disorders (MIND) Institute and the University of California, Irvine Alzheimer’s Disease Research Center (UCI-ADRC; NIA P50 AG16573). Research on miRNA in the Lukiw laboratory involving the microbiome and innate-immune responses in AD, amyloidogenesis, and neuroinflammation was supported through a COBRE III Pilot Project NIH/NIGMS grant P30-GM103340, an unrestricted grant to the LSU Eye Center from Research to Prevent Blindness (RPB); the Louisiana Biotechnology Research Network (LBRN) and NIH grants NEI EY006311, NIA AG18031, and NIA AG038834.


  1. 1.
    Jiang C, Li G, Huang P, Liu Z, Zhao B (2017) The gut microbiota and Alzheimer’s disease. J Alzheimers Dis 2017(58):1–15. CrossRefGoogle Scholar
  2. 2.
    Luan H, Wang X, Cai Z (2017) Mass spectrometry-based metabolomics: targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders. Mass Spectrom Rev.
  3. 3.
    Marizzoni M, Provasi S, Cattaneo A, Frisoni GB (2017) Microbiota and neurodegenerative diseases. Curr Opin Neurol 30:630–638. CrossRefPubMedGoogle Scholar
  4. 4.
    Quigley EMM (2017) Microbiota-brain-gut axis and neurodegenerative diseases. Curr Neurol Neurosci Rep 17:94. CrossRefPubMedGoogle Scholar
  5. 5.
    Westfall S, Lomis N, Kahouli I, Dia SY, Singh SP, Prakash S (2017) Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis. Cell Mol Life Sci 74:3769–3787. CrossRefPubMedGoogle Scholar
  6. 6.
    Zhu X, Han Y, Du J, Liu R, Jin K, Yi W (2017) Microbiota-gut-brain axis and the central nervous system. Oncotarget 8:53829–53838. PubMedPubMedCentralGoogle Scholar
  7. 7.
    Zhao Y, Cong L, Jaber V, Lukiw WJ (2017a) Microbiome-derived lipopolysaccharide enriched in the perinuclear region of Alzheimer’s disease brain. Front Immunol 8:1064. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zhao Y, Jaber V, Lukiw WJ (2017b) Secretory products of the human GI tract microbiome and their potential impact on Alzheimer’s disease (AD): detection of lipopolysaccharide (LPS) in AD hippocampus. Front Cell Infect Microbiol 7:318. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zhao Y, Cong L, Lukiw WJ (2017c) Lipopolysaccharide (LPS) accumulates in neocortical neurons of Alzheimer’s disease (AD) brains and impairs transcription in human neuronal-glial primary co-cultures. Front Aging Neurosci.
  10. 10.
    Bhattacharjee S, Lukiw WJ (2013) Alzheimer’s disease and the microbiome. Front Cell Neurosci 7:153. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hill JM, Clement C, Pogue AI, Bhattacharjee S, Zhao Y, Lukiw WJ (2014) Pathogenic microbes, the microbiome, and Alzheimer’s disease (AD). Front Aging Neurosci 6(127).
  12. 12.
    Perez HJ, Menezes ME, d'Acâmpora AJ (2014) Intestinal microbiota. Acta Gastroenterol Latinoam 44:265–272PubMedGoogle Scholar
  13. 13.
    Potgieter M, Bester J, Kell DB, Pretorius E (2015) The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev 39:567–591. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Zhao Y, Lukiw WJ (2015) Microbiome-generated amyloid and potential impact on amyloidogenesis in Alzheimer’s disease (AD). J Nat Sci 1:e138PubMedPubMedCentralGoogle Scholar
  15. 15.
    Alkasir R, Li J, Li X, Jin M, Zhu B (2016) Human gut microbiota: the links with dementia development. Protein Cell 8:90–102. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ghaisas S, Maher J, Kanthasamy A (2016) Gut microbiome in health and disease: linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacol Ther 158:52–62. CrossRefPubMedGoogle Scholar
  17. 17.
    Hu X, Wang T, Jin F (2016) Alzheimer’s disease and gut microbiota. Sci China Life Sci 59:1006–1023. CrossRefPubMedGoogle Scholar
  18. 18.
    Lukiw WJ (2016) The microbiome, microbial-generated proinflammatory neurotoxins, and Alzheimer’s disease. J Sport Health Sci 5:393–396. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Pistollato F, Sumalla-Cano S, Elio I, Masias Vergara M, Giampieri F, Battino M (2016) Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. Nutr Rev 74:624–634. CrossRefPubMedGoogle Scholar
  20. 20.
    Scheperjans F. (2016). Can microbiota research change our understanding of neurodegenerative diseases? Neurodegener. Dis. Manag 2016; 6:81–85.
  21. 21.
    Vogt NM, Kerby RL, Dill-McFarland KA, Harding S, Merluzzi AP, Johnson SC et al (2017) Gut microbiome alterations in Alzheimer’s disease. Sci Rep 7:13537. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zhao Y, Cong L, Lukiw WJ (2017) Plant and animal microRNAs (miRNAs) and their potential for inter-kingdom communication. Cell Mol Neurobiol 38:133–140. CrossRefPubMedGoogle Scholar
  23. 23.
    Bhattacharjee S, Zhao Y, Dua P, Rogaev EI, Lukiw WJ (2016) microRNA-34a-mediated down-regulation of the microglial-enriched triggering receptor and phagocytosis-sensor TREM2 in age-related macular degeneration. PLoS One 11:e0150211. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Lukiw WJ (2016) Bacteroides fragilis lipopolysaccharide and inflammatory signaling in Alzheimer’s disease (AD). Front Microbiol 7:1544CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Zhan LS, Davies SS (2016) Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions. Genome Med 8:46. CrossRefGoogle Scholar
  26. 26.
    Zhan X, Stamova B, Jin LW, DeCarli C, Phinney B, Sharp FR (2016) Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology 87:2324–2332. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Dendooven T, Luisi BF (2017) RNA search engines empower the bacterial intranet. Biochem Soc Trans:BST20160373.
  28. 28.
    Negi S, Singh H, Mukhopadhyay A (2017) Gut bacterial peptides with autoimmunity potential as environmental trigger for late onset complex diseases: in-silico study. PLoS One 12(7):e0180518. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Li D, Yu F (2017) Peripheral inflammatory biomarkers and cognitive decline in older adults with and without Alzheimer’s disease: a systematic review. J Gerontol Nurs 43:1–7. CrossRefGoogle Scholar
  30. 30.
    Choi HH, Cho YS (2016) Fecal microbiota transplantation: current applications, effectiveness, and future perspectives. Clin Endosc 49:257–265. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Pinti M, Appay V, Campisi J, Frasca D, Fülöp T, Sauce D et al (2016) Aging of the immune system: focus on inflammation and vaccination. Eur J Immunol 46:2286–2301. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Todar K (2016) Textbook of Bacteriology. available online at:
  33. 33.
    Abd Elmageed ZY, Naura AS, Errami Y, Zerfaoui M (2012) The poly(ADP-ribose) polymerases (PARPs): new roles in intracellular transport. Cell Signal 24:1–8. CrossRefPubMedGoogle Scholar
  34. 34.
    Tao X, Chen X, Hou Z, Hao S, Liu B (2017) Protective functions of PJ34, a poly(ADP-ribose) polymerase inhibitor, are related to down-regulation of calpain and nuclear factor-κB in a mouse model of traumatic brain injury. World Neurosurg 107:888–899. CrossRefPubMedGoogle Scholar
  35. 35.
    Wencel PL, Lukiw WJ, Strosznajder JB, Strosznajder RP (2017) Inhibition of poly(ADP-ribose) polymerase-1 enhances gene expression of selected sirtuins and APP cleaving enzymes in amyloid beta cytotoxicity. Mol Neurobiol.
  36. 36.
    Torres-Martínez S, Ruiz-Vázquez RM (2017) The RNAi universe in fungi: a varied landscape of small RNAs and biological functions. Annu Rev Microbiol 71:371–391. CrossRefPubMedGoogle Scholar
  37. 37.
    Varatharaj A, Galea I (2017) The blood-brain barrier in systemic inflammation. Brain Behav Immun 60:1–12. CrossRefPubMedGoogle Scholar
  38. 38.
    Pogue AI, Lukiw WJ (2018) Up-regulated pro-inflammatory microRNAs (miRNAs) in Alzheimer’s disease (AD) and age-related macular degeneration (AMD). Cell Mol Neurobiol.
  39. 39.
    Marcello E, Di Luca M, Gardoni F (2018) Synapse-to-nucleus communication: from developmental disorders to Alzheimer’s disease. Curr Opin Neurobiol 48:160–166. CrossRefPubMedGoogle Scholar
  40. 40.
    Alexandrov PN, Zhao Y, Jaber V, Cong L, Lukiw WJ (2017) Deficits in the proline-rich synapse-associated SHANK3 protein in multiple neuropsychiatric disorders. Front Neurol 8:670. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Mecca C, Giambanco I, Donato R, Arcuri C (2018) Microglia and aging: the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes. Int J Mol Sci ;19(1). doi:
  42. 42.
    Condello C, Yuan P, Grutzendler J (2018) Microglia-mediated neuroprotection, TREM2, and Alzheimer’s disease: evidence from optical imaging. Biol Psychiatry 83:377–387. CrossRefPubMedGoogle Scholar
  43. 43.
    Zhao Y, Lukiw WJ (2013) TREM2 signaling, miRNA-34a and the extinction of phagocytosis. Front Cell Neurosci 7:131. PubMedPubMedCentralGoogle Scholar
  44. 44.
    Lukiw WJ, Alexandrov PN (2012) Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer’s disease (AD) brain. Mol Neurobiol 46:11–19 ReviewCrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Seipold L, Saftig P (2016) The emerging role of tetraspanins in the proteolytic processing of the amyloid precursor protein. Front Mol Neurosci 9:149. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Li YY, Cui JG, Dua P, Pogue AI, Bhattacharjee S, Lukiw WJ (2011) Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural, astroglial and microglial cells. Neurosci Lett 499:109–113. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Swasthi HM, Mukhopadhyay S (2017) Electrostatic lipid-protein interactions sequester the curli amyloid fold on the lipopolysaccharide membrane surface. J Biol Chem 292:19861–19872. CrossRefPubMedGoogle Scholar
  48. 48.
    Pretorius E, Page MJ, Hendricks L, Nkosi NB, Benson SR, Kell DB (2018) Both lipopolysaccharide and lipoteichoic acids potently induce anomalous fibrin amyloid formation: assessment with novel Amytracker™ stains. J R Soc Interface ; 15. doi:
  49. 49.
    Sherwin E, Dinan TG, Cryan JF (2017) Recent developments in understanding the role of the gut microbiota in brain health and disease. Ann N Y Acad Sci.
  50. 50.
    Caballero-Villarraso J, Galvan A, Escribano BM, Túnez I (2017) Interrelationships between gut microbiota and host: paradigms, role in neurodegenerative diseases and future prospects. CNS Neurol Disord Drug Targets.
  51. 51.
    Bush K, Bradford PA (2016) β-lactams and β-lactamase inhibitors: an overview. Cold Spring Harb Perspect Med 6:a025247. CrossRefPubMedGoogle Scholar
  52. 52.
    Keenan JI, Aitchison A, Purcell RV, Greenlees R, Pearson JF, Frizelle FA (2016) Screening for enterotoxigenic Bacteroides fragilis in stool samples. Anaerobe 40:50–53. CrossRefPubMedGoogle Scholar
  53. 53.
    Fernando WMADB, Flint SH, Ranaweera KKDS, Bamunuarachchi A, Johnson SK, Brennan CS (2017) The potential synergistic behaviour of inter- and intra-genus probiotic combinations in the pattern and rate of short chain fatty acids formation during fibre fermentation. Int J Food Sci Nutr.
  54. 54.
    Choi VM, Herrou J, Hecht AL, Teoh WP, Turner JR, Crosson S et al (2016) Activation of Bacteroides fragilis toxin by a novel bacterial protease contributes to anaerobic sepsis. Nat Med 22:563–567. CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Fathi P, Wu S (2016) Isolation, detection and characterization of enterotoxigenic Bacteroides fragilis in clinical samples. Open Microbiol J 10:57–63. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C et al (2017) Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging 49:60–68. CrossRefPubMedGoogle Scholar
  57. 57.
    Shivaji S (2017) We are not alone: a case for the human microbiome in extra intestinal diseases. Gut Pathog 9:13. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Agrawal M, Ajazuddin, Tripathi DK, Saraf S, Saraf S, Antimisiaris SG et al (2017) Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer’s disease. J Control Release 260:61–77. CrossRefPubMedGoogle Scholar
  59. 59.
    Leshchyns'ka I, Sytnyk V (2016) Synaptic cell adhesion molecules in Alzheimer’s disease. Neural Plast 6427537.
  60. 60.
    Heinritz SN, Weiss E, Eklund M, Aumiller T, Heyer CM, Messner S et al (2016) Impact of a high-fat or high-fiber diet on intestinal microbiota and metabolic markers in a pig model. Nutrients 8:E317. CrossRefPubMedGoogle Scholar
  61. 61.
    Magata F, Shimizu T (2017) Effect of lipopolysaccharide on developmental competence of oocytes. Reprod Toxicol 71:1–7. CrossRefPubMedGoogle Scholar
  62. 62.
    Sears CL, Geis AL, Housseau F (2014) Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J Clin Invest 124:4166–4172. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z et al (2015) Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85:296–302. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Montagne A, Zhao Z, Zlokovic BV (2017) Alzheimer’s disease: a matter of blood-brain barrier dysfunction? J Exp Med 214:3151–3169. PubMedGoogle Scholar
  65. 65.
    Shoemark DK, Allen SJ (2015) The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer’s disease. J Alzheimers Dis 43:725–738. PubMedGoogle Scholar
  66. 66.
    Seong E, Yuan L, Arikkath J (2015) Cadherins and catenins in dendrite and synapse morphogenesis. Cell Adhes Migr 9:202–213. CrossRefGoogle Scholar
  67. 67.
    Dilling C, Roewer N, Förster CY, Burek M (2017) Multiple protocadherins are expressed in brain microvascular endothelial cells and might play a role in tight junction protein regulation. J Cereb Blood Flow Metab 37:3391–3400. CrossRefPubMedGoogle Scholar
  68. 68.
    Lin CS, Chang CJLCC, Martel J, Ojcius DM, Ko YF et al (2014) Impact of the gut microbiota, prebiotics, and probiotics on human health and disease. Biom J 37:259–268. Google Scholar
  69. 69.
    Bagyinszky E, Giau VV, Shim K, Suk K, An SSA, Kim S (2017) Role of inflammatory molecules in the Alzheimer’s disease progression and diagnosis. J Neurol Sci 376:242–254. CrossRefPubMedGoogle Scholar
  70. 70.
    Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39:73–82CrossRefPubMedGoogle Scholar
  71. 71.
    Sawikr Y, Yarla NS, Peluso I, Kamal MA, Aliev G, Bishayee A (2017) Neuroinflammation in Alzheimer’s disease: the preventive and therapeutic potential of polyphenolic nutraceuticals. Adv Protein Chem Struct Biol 108:33–57 2017CrossRefPubMedGoogle Scholar
  72. 72.
    Srivastava S, Singh D, Patel S, Singh MR (2017) Role of enzymatic free radical scavengers in management of oxidative stress in autoimmune disorders. Int J Biol Macromol 101:502–517. CrossRefPubMedGoogle Scholar
  73. 73.
    Jaber V, Zhao Y, Lukiw WJ (2017) Alterations in micro RNA-messenger RNA (miRNA-mRNA) coupled signaling networks in sporadic Alzheimer’s disease (AD) hippocampal CA1. J Alzheimers Dis Parkinsonism; 7(2). doi:
  74. 74.
    Hofer U (2014) Microbiome: B. fragilis and the brain. Nat Rev Microbiol 12:76–77. CrossRefPubMedGoogle Scholar
  75. 75.
    Keaney J, Campbell M (2015) The dynamic blood-brain barrier. FEBS J 282:4067–4079. CrossRefPubMedGoogle Scholar
  76. 76.
    Lloyd-Price J, Abu-Ali G, Huttenhower C (2016) The healthy human microbiome. Genome Med 8(51):51. CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Forner S, Baglietto-Vargas D, Martini AC, Trujillo-Estrada L, LaFerla FM (2017) Synaptic impairment in Alzheimer’s disease: a dysregulated symphony. Trends Neurosci 40:347–357. CrossRefPubMedGoogle Scholar
  78. 78.
    Ghosal A (2017) Importance of secreted bacterial RNA in bacterial-host interactions in the gut. Microb Pathog 104:161–163. CrossRefPubMedGoogle Scholar
  79. 79.
    Hill JM, Lukiw WJ (2016) microRNA-SHANK3-mediated pathogenetic signaling in Alzheimer’s disease (AD). Neurochem Res 41:96–100. CrossRefPubMedGoogle Scholar
  80. 80.
    Park JC, Baik SH, Han SH, Cho HJ, Choi H, Kim HJ, Choi H, Lee W et al (2017) Annexin A1 restores Aβ42-induced blood-brain barrier disruption through the inhibition of RhoA-ROCK signaling pathway. Aging Cell 16:149–161. CrossRefPubMedGoogle Scholar
  81. 81.
    Hill JM, Lukiw WJ (2015) Microbial-generated amyloids and Alzheimer’s disease (AD). Front Aging Neurosci 7(9).
  82. 82.
  83. 83.
    Lane CA, Hardy J, Schott JM (2017) Alzheimer’s disease. Eur J Neurol 25:59–70. CrossRefPubMedGoogle Scholar
  84. 84.
    Clark IA, Vissel B (2015) Amyloid β: one of three danger-associated molecules that are secondary inducers of the proinflammatory cytokines that mediate Alzheimer’s disease. Br J Pharmacol 172:3714–3727. CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Jiang Q, Jin S, Jiang Y, Liao M, Feng R, Zhang L, Liu G, Hao J (2017) Alzheimer’s disease variants with the genome-wide significance are significantly enriched in immune pathways and active in immune cells. Mol Neurobiol 54:594–600. CrossRefPubMedGoogle Scholar
  86. 86.
    Köhler CA, Maes M, Slyepchenko A, Berk M, Solmi M, Lanctôt KL, Carvalho A (2016) The gut-brain axis, including the microbiome, leaky gut and bacterial translocation: mechanisms and pathophysiological role in Alzheimer’s disease. Curr Pharm Des 22:6152–6166. CrossRefPubMedGoogle Scholar
  87. 87.
    Alzheimer’s disease facts and figures (2017);; Center for Disease Control (CDC; Accessed 12 Jan 2018);

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Authors and Affiliations

  1. 1.LSU Neuroscience CenterLouisiana State University Health Sciences CenterNew OrleansUSA
  2. 2.Department of Cell Biology and AnatomyLouisiana State University Health Sciences CenterNew OrleansUSA
  3. 3.Department of NeurologyLouisiana State University Health Sciences CenterNew OrleansUSA
  4. 4.Departments of OphthalmologyLouisiana State University Health Sciences CenterNew OrleansUSA

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