Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease

Nutrition Reviews

Volumn 74, Issue 10, 2016, Pages 624-634

  Pistollato, Francesca ^a   Cano, Sandra Sumalla ^a,b   Elio, Iñaki ^a,b   Vergara, Manuel Masias ^c   Giampieri, Francesca ^a,d   Battino, Maurizio ^a  

^a Parque Científico y Tecnológico de Cantabria   (Spain)

^b Universidad Internacional Iberoamericana   (Spain)

^c Universidad Internacional Iberoamericana (UNINI)   (Puerto Rico)

^d UNIVERSITÀ POLITECNICA DELLE MARCHE   (Italy)

Author keywords

Alzheimer disease; Amyloids; Bacteria; Diet; Gut microbiota; Gut brain axis; Prion like proteins

Indexed keywords

AMYLOID; AMYLOID PROTEIN; CYTOKINE; PREBIOTIC AGENT;

ALZHEIMER DISEASE; ARTICLE; BRAIN FUNCTION; DIET; GUT BRAIN AXIS; HUMAN; INTESTINE FLORA; NUTRIENT; PATHOGENESIS; PROTEIN FUNCTION; BACTERIUM; BIOSYNTHESIS; BRAIN; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY;

ALZHEIMER DISEASE; AMYLOID; BACTERIA; BRAIN; CYTOKINES; DIET; GASTROINTESTINAL MICROBIOME; HUMANS; PREBIOTICS;

EID: 84994505162     PISSN: 00296643     EISSN: 17534887     Source Type: Journal    
DOI: 10.1093/nutrit/nuw023     Document Type: Article

References (176)

1. Petra AI, Panagiotidou S, Hatziagelaki E, et al. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther. 2015;37:984-995.
2. Burokas A, Moloney RD, Dinan TG, et al. Microbiota regulation of the mammalian gut-brain axis. Adv Appl Microbiol. 2015;91:1-62.
3. Stecher B. The roles of inflammation, nutrient availability and the commensal microbiota in enteric pathogen infection. Microbiol Spectr. 2015;3:1-17.
4. Bekkering P, Jafri I, van Overveld FJ, et al. The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes. Expert Rev Clin Immunol. 2013;9:1031-1041.
5. Esteve E, Ricart W, Fernandez-Real JM. Gut microbiota interactions with obesity, insulin resistance and type 2 diabetes: did gut microbiote co-evolve with insulin resistance? Curr Opin Clin Nutri Metabol Care. 2011;14:483-490.
6. Mager I, Roberts TC, Wood MJ, et al. From gut to brain: bioencapsulated therapeutic protein reduces amyloid load upon oral delivery. Mol Therapy. 2014;22:485-486.
7. Hao K, Di Narzo AF, Ho L, et al. Shared genetic etiology underlying alzheimer's disease and type 2 diabetes. Mol Aspects Med. 2015;43-44:66-76.
8. Dai Y, Kamal MA. Fighting Alzheimer's disease and type 2 diabetes: pathological links and treatment strategies. CNS Neurol Disord Drug Targets. 2014;13:271-282.
9. de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol. 2014;88:548-559.
10. Zhao Y, Dua P, Lukiw WJ. Microbial sources of amyloid and relevance to amyloidogenesis and Alzheimer's disease (AD). J Alzheimer's Dis Parkinsonism. 2015;5:177. doi:10.4172/2161-0460.1000177.
11. Bhattacharjee S, Lukiw WJ. Alzheimer's disease and the microbiome. Front Cell Neurosci. 2013;7:153. doi:10.3389/fncel.2013.00153.
12. Syed AK, Boles BR. Fold modulating function: bacterial toxins to functional amyloids. Front Microbiol. 2014;5:401. doi:10.3389/fmicb.2014.00401.
13. Hufnagel DA, Tukel C, Chapman MR. Disease to dirt: the biology of microbial amyloids. PLoS Pathog. 2013;9:e1003740. doi:10.1371/journal.ppat.1003740.
14. Schwartz K, Boles BR. Microbial amyloids-functions and interactions within the host. Curr Opin Microbiol. 2013;16:93-99.
15. Oli MW, Otoo HN, Crowley PJ, et al. Functional amyloid formation by Streptococcus mutans. Microbiology. 2012;158(pt 12):2903-2916.
16. Friedland RP. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration. J Alzheimers Dis. 2015;45:349-362.
17. Scott KP, Gratz SW, Sheridan PO, et al. The influence of diet on the gut microbiota. Pharmacol Res. 2013;69:52-60.
18. Soto C. Transmissible proteins: expanding the prion heresy. Cell. 2012;149:968-977.
19. Berti V, Murray J, Davies M, et al. Nutrient patterns and brain biomarkers of Alzheimer's disease in cognitively normal individuals. J Nutr Health Aging. 2015;19:413-423.
20. Stefani M, Rigacci S. Beneficial properties of natural phenols: highlight on protection against pathological conditions associated with amyloid aggregation. BioFactors. 2014;40:482-493.
21. Rigacci S, Stefani M. Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols. Expert Rev Neurother. 2015;15:41-52.
22. Bastianetto S, Krantic S, Quirion R. Polyphenols as potential inhibitors of amyloid aggregation and toxicity: possible significance to Alzheimer's disease. Mini Rev Med Chem. 2008;8:429-435.
23. Bieschke J, Russ J, Friedrich RP, et al. EGCG remodels mature α-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Proc Natl Acad Sci U S A. 2010;107:7710-7715.
24. Carabotti M, Scirocco A, Maselli MA, et al. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28:203-209.
25. Daulatzai MA. Chronic functional bowel syndrome enhances gut-brain axis dysfunction, neuroinflammation, cognitive impairment, and vulnerability to dementia. Neurochem Res. 2014;39:624-644.
26. Ano Y, Sakudo A, Nakayama H, et al. Uptake and dynamics of infectious prion protein in the intestine. Protein Pept Lett. 2009;16:247-255.
27. Kraus A, Groveman BR, Caughey B. Prions and the potential transmissibility of protein misfolding diseases. Annu Rev Microbiol. 2013;67:543-564.
28. Prusiner SB. Cell biology. A unifying role for prions in neurodegenerative diseases. Science. 2012;336:1511-1513.
29. Walker LC, Jucker M. Neurodegenerative diseases: expanding the prion concept. Annu Rev Neurosci. 2015;38:87-103.
30. Yoshioka H, Takeda T, Higuchi K, et al. Immunohistochemical examination of Peyer's patches in senescence-accelerated mice. Autoimmunity. 1990;8:25-35.
31. Ano Y, Nakayama H, Sakudo A, et al. Intestinal uptake of amyloid b protein through columnar epithelial cells in suckling mice. Histol Histopathol. 2009;24:283-292.
32. Solomon A, Richey T, Murphy CL, et al. Amyloidogenic potential of foie gras. Proc Natl Acad Sci U S A. 2007;104:10998-11001.
33. Ali-Khan Z, Normand J, Alizadeh-Khiavi K, et al. Ubiquitin profile and amyloid enhancing factor activity in Alzheimer and 'normal' human brain extracts. Neurosci Lett. 1992;139:24-28.
34. Urieli-Shoval S, Cohen P, Eisenberg S, et al. Widespread expression of serum amyloid A in histologically normal human tissues. Predominant localization to the epithelium. J Histochem Cytochem. 1998;46:1377-1384.
35. Kindy MS, Yu J, Guo JT, et al. Apolipoprotein serum amyloid A in Alzheimer's disease. J Alzheimer's Dis. 1999;1:155-167.
36. Liang JS, Sloane JA, Wells JM, et al. Evidence for local production of acute phase response apolipoprotein serum amyloid A in Alzheimer's disease brain. Neurosci Lett. 1997;225:73-76.
37. Yu Y, Liu J, Li SQ, et al. Serum amyloid a differentially activates microglia and astrocytes via the PI3K pathway. J Alzheimers Dis. 2014;38:133-144.
38. Delzenne NM, Cani PD, Everard A, et al. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia. 2015. doi:10.1007/s00125-015-3712-7.
39. Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136:65-80.
40. Campbell AW. Autoimmunity and the gut. Autoimmune Dis. 2014;2014:152428. doi:10.1155/2014/152428.
41. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13:701-712.
42. Trasande L, Blustein J, Liu M, et al. Infant antibiotic exposures and early-life body mass. Int J Obes. 2013;37:16-23.
43. Hicks LA, Taylor TH Jr, Hunkler RJ. U.S. outpatient antibiotic prescribing, 2010. N Engl J Med. 2013;368:1461-1462.
44. Vangay P, Ward T, Gerber JS, et al. Antibiotics, pediatric dysbiosis, and disease. Cell Host Microbe. 2015;17:553-564.
45. Muegge BD, Kuczynski J, Knights D, et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science. 2011;332:970-974.
46. Delzenne NM, Neyrinck AM, Cani PD. Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome. Microbial Cell Factories. 2011;10(suppl 1):S10. doi:10.1186/1475-2859-10-S1-S10.
47. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514:181-186.
48. Bjorklund M, Ouwehand AC, Forssten SD, et al. Gut microbiota of healthy elderly NSAID users is selectively modified with the administration of Lactobacillus acidophilus NCFM and lactitol. Age. 2012;34:987-999.
49. Shen J, Obin MS, Zhao L. The gut microbiota, obesity and insulin resistance. Mol Aspects Med. 2013;34:39-58.
50. Daulatzai MA. Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia. CNS Neurol Disord Drug Targets. 2015;14:110-131.
51. Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship. Gut. 2014;63:1513-1521.
52. Rosenfeld CS. Microbiome disturbances and autism spectrum disorders. Drug Metabol Dispos. 2015;43:1557-1571.
53. Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014;38:1-12.
54. Lai SW, Liao KF, Lin CL, et al. Irritable bowel syndrome correlates with increased risk of Parkinson's disease in Taiwan. Eur J Epidemiol. 2014;29:57-62.
55. Rhee SH. Lipopolysaccharide: basic biochemistry, intracellular signaling, and physiological impacts in the gut. Intest Res. 2014;12:90-95.
56. Ding PH, Jin LJ. The role of lipopolysaccharide-binding protein in innate immunity: a revisit and its relevance to oral/periodontal health. J Periodontal Res. 2014;49:1-9.
57. Asti A, Gioglio L. Can a bacterial endotoxin be a key factor in the kinetics of amyloid fibril formation? J Alzheimers Dis. 2014;39:169-179.
58. Morales R, Moreno-Gonzalez I, Soto C. Cross-seeding of misfolded proteins: implications for etiology and pathogenesis of protein misfolding diseases. PLoS Pathog. 2013;9:e1003537. doi:10.1371/journal.ppat.1003537.
59. Shoemark DK, Allen SJ. The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer's disease. J Alzheimers Dis. 2015;43:725-738.
60. Tran L, Greenwood-Van Meerveld B. Age-associated remodeling of the intestinal epithelial barrier. J Gerontol. Series A Biol Sci Med Sci. 2013;68:1045-1056.
61. Marques F, Sousa JC, Sousa N, et al. Blood-brain-barriers in aging and in Alzheimer's disease. Mol Neurodegener. 2013;8:38. doi:10.1186/1750-1326-8-38.
62. Zhao Y, Lukiw WJ. Microbiome-generated amyloid and potential impact on amyloidogenesis in Alzheimer's disease (AD). J Nat Sci. 2015;1:e138.
63. Hammer ND, Wang X, McGuffie BA, et al. Amyloids: friend or foe? J Alzheimer's Dis. 2008;13:407-419.
64. Blanco LP, Evans ML, Smith DR, et al. Diversity, biogenesis and function of microbial amyloids. Trends Microbiol. 2012;20:66-73.
65. Daulatzai MA. Role of stress, depression, and aging in cognitive decline and Alzheimer's disease. Curr Topics Behav Neurosci. 2014;18:265-296.
66. Naseer MI, Bibi F, Alqahtani MH, et al. Role of gut microbiota in obesity, type 2 diabetes and Alzheimer's disease. CNS Neurol Disord Drug Targets. 2014;13:305-311.
67. Alam MZ, Alam Q, Kamal MA, et al. A possible link of gut microbiota alteration in type 2 diabetes and Alzheimer's disease pathogenicity: an update. CNS Neurol Disords Drug Targets. 2014;13:383-390.
68. Hill JM, Lukiw WJ. Microbial-generated amyloids and Alzheimer's disease (AD). Front Aging Neurosci. 2015;7:9. doi:10.3389/fnagi.2015.00009.
69. Deane R, Du Yan S, Submamaryan RK, et al. RAGE mediates amyloid-b peptide transport across the blood-brain barrier and accumulation in brain. Nat Med. 2003;9:907-913.
70. Zlokovic BV. Cerebrovascular transport of Alzheimer's amyloid b and apolipoproteins J and E: possible anti-amyloidogenic role of the blood-brain barrier. Life Sci. 1996;59:1483-1497.
71. Deane R, Wu Z, Sagare A, et al. LRP/amyloid β-peptide interaction mediates differential brain efflux of Ab isoforms. Neuron. 2004;43:333-344.
72. Weiss N, Miller F, Cazaubon S, et al. The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta. 2009;1788:842-857.
73. Viegas P, Chaverot N, Enslen H, et al. Junctional expression of the prion protein PrPC by brain endothelial cells: a role in trans-endothelial migration of human monocytes. J Cell Sci. 2006;119(pt 22):4634-4643.
74. Perez Martinez G, Bauerl C, Collado MC. Understanding gut microbiota in elderly's health will enable intervention through probiotics. Benef Microbes. 2014;5:235-246.
75. Rehman T. Role of the gut microbiota in age-related chronic inflammation. Endocr Metab Immune Disord Drug Targets. 2012;12:361-367.
76. Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178-184.
77. Zhao Y, Lukiw WJ. TREM2 signaling, miRNA-34a and the extinction of phagocytosis. Front Cell Neurosci. 2013;7:131. doi:10.3389/fncel.2013.00131.
78. Zhang J, Ke KF, Liu Z, et al. Th17 cell-mediated neuroinflammation is involved in neurodegeneration of ab1-42-induced Alzheimer's disease model rats. PLoS One. 2013;8:e75786. doi:10.1371/journal.pone.0075786.
79. Aziz Q, Dore J, Emmanuel A, et al. Gut microbiota and gastrointestinal health: current concepts and future directions. Neurogastroenterol Motility. 2013;25:4-15.
80. Hornig M. The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol. 2013;25:488-795.
81. Mitew S, Kirkcaldie MT, Dickson TC, et al. Altered synapses and gliotransmission in Alzheimer's disease and AD model mice. Neurobiol Aging. 2013;34:2341-2351.
82. Paula-Lima AC, Brito-Moreira J, Ferreira ST. Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease. J Neurochem. 2013;126:191-202.
83. Bienenstock J, Kunze W, Forsythe P. Microbiota and the gut-brain axis. Nutr Rev. 2015;73(suppl 1):28-31.
84. Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015;11:577-591.
85. Alvarez A, Aleixandre M, Linares C, et al. Apathy and APOE4 are associated with reduced BDNF levels in Alzheimer's disease. J Alzheimers Dis. 2014;42:1347-1355.
86. Carlino D, De Vanna M, Tongiorgi E. Is altered BDNF biosynthesis a general feature in patients with cognitive dysfunctions? Neuroscientist. 2013;19:345-353.
87. Bercik P, Denou E, Collins J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141:599.e3-609.e3.
88. Fontaine CA, Skorupski AM, Vowles CJ, et al. How free of germs is germ-free? Detection of bacterial contamination in a germ free mouse unit. Gut Microbes. 2015;6:225-233.
89. Packey CD, Shanahan MT, Manick S, et al. Molecular detection of bacterial contamination in gnotobiotic rodent units. Gut Microbes. 2013;4:361-370.
90. Chung H, Pamp SJ, Hill JA, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012;149:1578-1593.
91. -/- mice. Infect Immun. 2014;82:2239-2246.
92. Nguyen TL, Vieira-Silva S, Liston A, et al. How informative is the mouse for human gut microbiota research? Dis Model Mech. 2015;8:1-16.
93. Lakhan SE, Caro M, Hadzimichalis N. NMDA receptor activity in neuropsychiatric disorders. Front Psychiatry. 2013;4:52. doi:10.3389/fpsyt.2013.00052.
94. Pablo J, Banack SA, Cox PA, et al. Cyanobacterial neurotoxin BMAA in ALS and Alzheimer's disease. Acta Neurol Scand. 2009;120:216-225.
95. Potgieter M, Bester J, Kell DB, et al. The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev. 2015;39:567-591.
96. Lipinski B, Pretorius E. The role of iron-induced fibrin in the pathogenesis of Alzheimer's disease and the protective role of magnesium. Front Hum Neurosci. 2013;7:735. doi:10.3389/fnhum.2013.00735.
97. Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain & behaviour-epigenetic regulation of the gut-brain axis. Genes Brain Behav. 2014;13:69-86.
98. Pistollato F. Role of dietary patterns in the prevention and regression of insulin resistance-related cancers. Med J Nutriton Metab. 2015;8:37-49.
99. Pistollato F, Battino M. Role of plant-based diets in the prevention and regression of metabolic syndrome and neurodegenerative diseases. Trends Food Sci Technol. 2014;40:62-81.
100. Stenvinkel P. Obesity-a disease with many aetiologies disguised in the same oversized phenotype: has the overeating theory failed? Nephrol Dial Transplant. 2015;30:1656-1564.
101. John S, Luben R, Shrestha SS, et al. Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study. Eur J Gastroenterol Hepatol. 2010;22:602-606.
102. Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006;83(6 suppl):1505S-1519S.
103. Calder PC. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res. 2008;52:885-897.
104. Connor WE, Connor SL. The importance of fish and docosahexaenoic acid in Alzheimer disease. Am J Clin Nutr. 2007;85:929-930.
105. Shinto L, Quinn J, Montine T, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease. J Alzheimers Dis. 2014;38:111-120.
106. Lorente-Cebrian S, Costa AG, Navas-Carretero S, et al. An update on the role of omega-3 fatty acids on inflammatory and degenerative diseases. J Physiol Biochem. 2015;71:341-349.
107. Greiner AK, Papineni RV, Umar S. Chemoprevention in gastrointestinal physiology and disease. Natural products and microbiome. Am J Physiol Gastrointest Liver Physiol. 2014;307:G1-G15.
108. De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107:14691-14696.
109. Simpson HL, Campbell BJ. Review article: dietary fibre-microbiota interactions. Aliment Pharmacol Ther. 2015;42:158-179.
110. Galland L. The gut microbiome and the brain. J Med Food. 2014;17:1261-1272.
111. Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013;6:39-51.
112. Fallucca F, Porrata C, Fallucca S, et al. Influence of diet on gut microbiota, inflammation and type 2 diabetes mellitus. First experience with macrobiotic Ma-Pi 2 diet. Diabetes Metab Res Rev. 2014;30(suppl 1):48-54.
113. Wang IK, Wu YY, Yang YF, et al. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial. Benef Microbes. 2015;6:423-430.
114. Rincon D, Vaquero J, Hernando A, et al. Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites. Liver Int. 2014;34:1504-1512.
115. de Gonzalo-Calvo D, Fernandez-Garcia B, de Luxan-Delgado B, et al. Long-term training induces a healthy inflammatory and endocrine emergent biomarker profile in elderly men. Age. 2012;34:761-771.
116. Gill HS, Rutherfurd KJ, Cross ML, et al. Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutr. 2001;74:833-839.
117. Tillisch K, Labus J, Kilpatrick L, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013;144: 1394.e4-1401.e4.
118. Tillisch K. The effects of gut microbiota on CNS function in humans. Gut Microbes. 2014;5:404-410.
119. Huck V, Schneider MF, Gorzelanny C, et al. The various states of von Willebrand factor and their function in physiology and pathophysiology. Thromb Haemost. 2014;111:598-609.
120. Tomasik J, Yolken RH, Bahn S, et al. Immunomodulatory effects of probiotic supplementation in schizophrenia patients: a randomized, placebo-controlled trial. Biomark Insights. 2015;10:47-54.
121. Kim MS, Hwang SS, Park EJ, et al. Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation. Environ Microbiol Rep. 2013;5:765-775.
122. Zhang J, Wu Y, Zhang Y, et al. The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Mol Endocrinol. 2008;22:1416-1426.
123. Mosconi L, Murray J, Davies M, et al. Nutrient intake and brain biomarkers of Alzheimer's disease in at-risk cognitively normal individuals: a cross-sectional neuroimaging pilot study. BMJ Open. 2014;4:e004850. doi:10.1136/bmjopen-2014-004850.
124. Rigacci S. Olive oil phenols as promising multi-targeting agents against Alzheimer's disease. Adv Exp Med Biol. 2015;863:1-20.
125. Abuznait AH, Qosa H, Busnena BA, et al. Olive-oil-derived oleocanthal enhances b-amyloid clearance as a potential neuroprotective mechanism against Alzheimer's disease: in vitro and in vivo studies. ACS Chem Neurosci. 2013;4:973-982.
126. Qosa H, Abuasal BS, Romero IA, et al. Differences in amyloid-b clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling. Neuropharmacology. 2014;79:668-678.
127. Ehrnhoefer DE, Bieschke J, Boeddrich A, et al. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat Struct Mol Biol. 2008;15:558-566.
128. Grelle G, Otto A, Lorenz M, et al. Black tea theaflavins inhibit formation of toxic amyloid-b andαsynuclein fibrils. Biochemistry. 2011;50:10624-10636.
129. Bastianetto S, Yao ZX, Papadopoulos V, et al. Neuroprotective effects of green and black teas and their catechin gallate esters against β-amyloid-induced toxicity. Eur J Neurosci. 2006;23:55-64.
130. Fernando WM, Martins IJ, Goozee KG, et al. The role of dietary coconut for the prevention and treatment of Alzheimer's disease: potential mechanisms of action. Br J Nutr. 2015;114:1-14.
131. Subash S, Essa MM, Braidy N, et al. Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer's disease. J Ayurveda Integr Med. 2015;6:111-120.
132. Liu Y, Pukala TL, Musgrave IF, et al. Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation. Bioorg Med Chem Lett. 2013;23:6336-6340.
133. Gupta VB, Indi SS, Rao KS. Garlic extract exhibits antiamyloidogenic activity on amyloid-beta fibrillogenesis: relevance to Alzheimer's disease. Phytother Res. 2009;23:111-115.
134. Chauhan N, Wang KC, Wegiel J, et al. Walnut extract inhibits the fibrillization of amyloid beta-protein, and also defibrillizes its preformed fibrils. Curr Alzheimer Res. 2004;1:183-188.
135. Lolicato F, Raudino A, Milardi D, et al. Resveratrol interferes with the aggregation of membrane-bound human-IAPP: a molecular dynamics study. Eur J Med Chem. 2015;92:876-881.
136. Evers F, Jeworrek C, Tiemeyer S, et al. Elucidating the mechanism of lipid membrane-induced IAPP fibrillogenesis and its inhibition by the red wine compound resveratrol: a synchrotron X-ray reflectivity study. J Am Chem Soc. 2009;131:9516-9521.
137. Hugel HM. Brain food for Alzheimer-free ageing: focus on herbal medicines. Adv Exp Med Biol. 2015;863:95-116.
138. Laparra JM, Sanz Y. Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res. 2010;61:219-225.
139. Lee HC, Jenner AM, Low CS, et al. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Res Microbiol. 2006;157:876-884.
140. Merkle DL, Cheng CH, Castellino FJ, et al. Modulation of fibrin assembly and polymerization by the beta-amyloid of Alzheimer's disease. Blood Coagul Fibrinolysis. 1996;7:650-658.
141. Zamolodchikov D, Strickland S. Ab delays fibrin clot lysis by altering fibrin structure and attenuating plasminogen binding to fibrin. Blood. 2012;119:3342-3351.
142. Hultman K, Strickland S, Norris EH. The APOE e4/e4 genotype potentiates vascular fibrin(ogen) deposition in amyloid-laden vessels in the brains of Alzheimer's disease patients. J Cereb Blood Flow Metab. 2013;33:1251-1258.
143. Friedland RP, Tedesco JM, Wilson AC, et al. Antibodies to potato virus Y bind the amyloid b peptide: immunohistochemical and NMR studies. J Biol Chem. 2008;283:22550-22556.
144. Liu R, Vaishnav RA, Roberts AM, et al. Humans have antibodies against a plant virus: evidence from tobacco mosaic virus. PLoS One. 2013;8:e60621. doi:10.1371/journal.pone.0060621.
145. Colussi TM, Costantino DA, Hammond JA, et al. The structural basis of transfer RNA mimicry and conformational plasticity by a viral RNA. Nature. 2014;511:366-369.
146. Rebolledo-Mendez JD, Vaishnav RA, Cooper NG, et al. Cross-kingdom sequence similarities between human micro-RNAs and plant viruses. Commun Integr Biol. 2013;6:e24951. doi:10.4161/cib.24951.
147. Pogue AI, Hill JM, Lukiw WJ. MicroRNA (miRNA): sequence and stability, viroidlike properties, and disease association in the CNS. Brain Res. 2014;1584:73-79.
148. Hill JM, Zhao Y, Bhattacharjee S, et al. miRNAs and viroids utilize common strategies in genetic signal transfer. Front Mol Neurosci. 2014;7:10. doi:10.3389/fnmol.2014.00010.
149. Cheng L, Quek CY, Sun X, et al. The detection of microRNA associated with Alzheimer's disease in biological fluids using next-generation sequencing technologies. Front Genet. 2013;4:150. doi:10.3389/fgene.2013.00150.
150. Alexandrov PN, Dua P, Hill JM, et al. microRNA (miRNA) speciation in Alzheimer's disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF). Int J Biochem Mol Biol. 2012;3:365-373.
151. Hill JM, Lukiw WJ. microRNA (miRNA)-Mediated pathogenetic signaling in Alzheimer's disease (AD). Neurochem Res. 2016;41:96-100.
152. Mattson MP. Will caloric restriction and folate protect against AD and PD? Neurology. 2003;60:690-695.
153. Willette AA, Johnson SC, Birdsill AC, et al. Insulin resistance predicts brain amyloid deposition in late middle-aged adults. Alzheimers Dement. 2015;11:504.e1-510.e1.
154. Kenna H, Hoeft F, Kelley R, et al. Fasting plasma insulin and the default mode network in women at risk for Alzheimer's disease. Neurobiol Aging. 2013;34:641-649.
155. Cherbuin N, Sachdev P, Anstey KJ. Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study. Neurology. 2012;79:1019-1026.
156. Blom K, Emmelot-Vonk MH, Koek HL. The influence of vascular risk factors on cognitive decline in patients with dementia: a systematic review. Maturitas. 2013;76:113-117.
157. Ferreira ST, Clarke JR, Bomfim TR, et al. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer's disease. Alzheimers Dement. 2014;10(1 suppl):S76-S83.
158. Morris JK, Vidoni ED, Honea RA, et al. Impaired glycemia increases disease progression in mild cognitive impairment. Neurobiol Aging. 2014;35:585-589.
159. Rosendorff C, Beeri MS, Silverman JM. Cardiovascular risk factors for Alzheimer's disease. Am J Geriatr Cardiol. 2007;16:143-149.
160. Strittmatter WJ, Saunders AM, Schmechel D, et al. Apolipoprotein E: high-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993;90:1977-1981.
161. Tanzi RE. TREM2 and risk of Alzheimer's disease-friend or foe? N Engl J Med. 2015;372:2564-2565.
162. Kohli N, Westerveld DR, Ayache AC, et al. Oral delivery of bioencapsulated proteins across blood-brain and blood-retinal barriers. Mol Therapy. 2014;22:535-546.
163. Fisher AE, Naughton DP. Why nutraceuticals do not prevent or treat Alzheimer's disease. Nutr J. 2005;4:14. doi:10.1186/1475-2891-4-14.
164. Carvalho BM, Guadagnini D, Tsukumo DM, et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia. 2012;55:2823-2834.
165. Daubioul C, Rousseau N, Demeure R, et al. Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats. J Nutr. 2002;132:967-973.
166. Cani PD, Possemiers S, Van de Wiele T, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009;58:1091-1103.
167. Everard A, Lazarevic V, Derrien M, et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptinresistant mice. Diabetes. 2011;60:2775-2786.
168. Petschow B, Dore J, Hibberd P, et al. Probiotics, prebiotics, and the host microbiome: the science of translation. Ann N Y Acad Sci. 2013;1306:1-17.
169. Pistollato F, Cavanaugh SE, Chandrasekera PC. A human-based integrated framework for Alzheimer's disease research. J Alzheimers Dis. 2015;47:857-868.
170. Langley GR. Considering a new paradigm for Alzheimer's disease research. Drug Discov Today. 2014;19:1114-1124.
171. Gutierrez-Orozco F, Thomas-Ahner JM, Berman-Booty LD, et al. Dietary a-mangostin, a xanthone from mangosteen fruit, exacerbates experimental colitis and promotes dysbiosis in mice. Mol Nutr Food Res. 2014;58:1226-1238.
172. Wang Y, Xia Z, Xu JR, et al.αMangostin, a polyphenolic xanthone derivative from mangosteen, attenuates β-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation. Neuropharmacology. 2012;62:871-881.
173. Park J, Lee BK, Jeong GS, et al. Three-dimensional brain-on-a-chip with an interstitial level of flow and its application as an in vitro model of Alzheimer's disease. Lab Chip. 2015;15:141-150.
174. Dinh ND, Chiang YY, Hardelauf H, et al. Microfluidic construction of minimalistic neuronal co-cultures. Lab Chip. 2013;13:1402-1412.
175. Kim HJ, Ingber DE. Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr Biol (Cambridge). 2013;5: 1130-1140.
176. Kim HJ, Huh D, Hamilton G, et al. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip. 2012;12:2165-2174.