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Polymicrobial Infections and Neurodegenerative Diseases

  • Infectious Involvement in Neurological Disease (B Balin, Section Editor)
  • Published:
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Abstract

Purpose of Review

Neurodegenerative diseases are a heterogeneous group of chronic disorders linked by the progressive degeneration of neurons in discrete regions of the central nervous system. Knowledge about the etiology of neurodegenerative diseases remains a major goal in modern medicinal research. In this review, we analyze and summarize the evidence for fungal and bacterial infections in the nervous tissue of patients with chronic neurodegenerative diseases.

Recent Findings

There is a growing body of evidence supporting the concept that polymicrobial infection could be the etiological agent for several neurodegenerative diseases. A variety of fungi and bacteria can be directly visualized in brain tissue from patients by immunohistochemistry using specific antibodies, and next-generation sequencing has recently revealed the identification of potentially causative microorganisms. Notably, the brain microbiota can vary from patient to patient, but importantly, some microbial genera are more relevant in a given disease.

Summary

Multiple experimental approaches have identified a diversity of fungal and prokaryotic populations in the central nervous system of patients with different neurodegenerative disorders. This diversity present in each patient could account for the differences in the severity and evolution of clinical symptoms.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Sweeney MD, Kisler K, Montagne A, Toga AW, Zlokovic BV. The role of brain vasculature in neurodegenerative disorders. Nat Neurosci. 2018;21(10):1318–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Al-Obaidi MMJ, Desa MNM. Mechanisms of blood brain barrier disruption by different types of bacteria, and bacterial-host interactions facilitate the bacterial pathogen invading the brain. Cell Mol Neurobiol. 2018;38(7):1349–68.

    CAS  PubMed  Google Scholar 

  3. McManus RM, Heneka MT. Role of neuroinflammation in neurodegeneration: new insights. Alzheimers Res Ther. 2017;9(1):14.

    PubMed  PubMed Central  Google Scholar 

  4. • Kumar DK, Choi SH, Washicosky KJ, Eimer WA, Tucker S, Ghofrani J, et al. Amyloid-beta peptide protects against microbial infection in mouse and worm models of Alzheimer's disease. Sci Transl Med. 2016;8(340):340ra72 This work demonstrates that amyloid is involved in the innate-immune system and protects against infection by fungi and bacteria.

    PubMed  Google Scholar 

  5. Hill JM, Lukiw WJ. Microbial-generated amyloids and Alzheimer’s disease (AD). Front Aging Neurosci. 2015;7:9.

    PubMed  PubMed Central  Google Scholar 

  6. Teich AF, Arancio O. Is the amyloid hypothesis of Alzheimer’s disease therapeutically relevant? Biochem J. 2012;446(2):165–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Golde TE, DeKosky ST, Galasko D. Alzheimer’s disease: the right drug, the right time. Science. 2018;362(6420):1250–1.

    CAS  PubMed  Google Scholar 

  8. Tam C, Wong JH, Ng TB, Tsui SK, Zuo T. Drugs for targeted therapies of Alzheimer’s disease. Curr Med Chem. 2018;26(2):335–59.

    Google Scholar 

  9. Little CS, Hammond CJ, MacIntyre A, Balin BJ, Appelt DM. Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice. Neurobiol Aging. 2004;25(4):419–29.

    CAS  PubMed  Google Scholar 

  10. Miklossy J, Arai T, Guo JP, Klegeris A, Yu S, McGeer EG, et al. LRRK2 expression in normal and pathologic human brain and in human cell lines. J Neuropathol Exp Neurol. 2006;65(10):953–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Dehhaghi M, Kazemi Shariat Panahi H, Guillemin GJ. Microorganisms’ footprint in neurodegenerative diseases. Front Cell Neurosci. 2018;12:466.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. •• Forbes JD, Bernstein CN, Tremlett H, Van Domselaar G, Knox NC. A fungal world: could the gut mycobiome be involved in neurological disease? Front Microbiol. 2018;9:3249 This manuscript revises the role of the gut mycobiota in neurodegenerative diseases.

    PubMed  Google Scholar 

  13. Tremlett H, Bauer KC, Appel-Cresswell S, Finlay BB, Waubant E. The gut microbiome in human neurological disease: a review. Ann Neurol. 2017;81(3):369–82.

    PubMed  Google Scholar 

  14. Eratne D, Loi SM, Farrand S, Kelso W, Velakoulis D, Looi JC. Alzheimer’s disease: clinical update on epidemiology, pathophysiology and diagnosis. Australas Psychiatry. 2018;26(4):347–57.

    PubMed  Google Scholar 

  15. Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Uchoa MF, Moser VA, Pike CJ. Interactions between inflammation, sex steroids, and Alzheimer’s disease risk factors. Front Neuroendocrinol. 2016;43:60–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Revett TJ, Baker GB, Jhamandas J, Kar S. Glutamate system, amyloid ss peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology. J Psychiatry Neurosci. 2013;38(1):6–23.

    PubMed  PubMed Central  Google Scholar 

  18. Labzin LI, Heneka MT, Latz E. Innate immunity and neurodegeneration. Annu Rev Med. 2018;69:437–49.

    CAS  PubMed  Google Scholar 

  19. Santos CY, Snyder PJ, Wu WC, Zhang M, Echeverria A, Alber J. Pathophysiologic relationship between Alzheimer’s disease, cerebrovascular disease, and cardiovascular risk: a review and synthesis. Alzheimers Dement (Amst). 2017;7:69–87.

    Google Scholar 

  20. • Ashraf GM, Tarasov VV. Makhmutovsmall a CA, Chubarev VN, Avila-Rodriguez M, Bachurin SO, et al. The possibility of an infectious etiology of Alzheimer disease. Mol Neurobiol. 2019;56(6):4479–91 In this review article, the potential role of bacteria, including spirochetes, fungi, and viral infections as potential causative agents of AD is revised. In addition, the antimicrobial activity of the amyloid peptide is also revised.

    CAS  PubMed  Google Scholar 

  21. •• Harris SA, Harris EA. Molecular mechanisms for herpes simplex virus type 1 pathogenesis in Alzheimer’s disease. Front Aging Neurosci. 2018;10:48 This article represents a comprehensive revision of a variety of microbes involved as etiological agents of AD.

    PubMed  PubMed Central  Google Scholar 

  22. Sochocka M, Zwolinska K, Leszek J. The infectious etiology of Alzheimer’s disease. Curr Neuropharmacol. 2017;15(7):996–1009.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Itzhaki RF. Herpes and Alzheimer’s disease: subversion in the central nervous system and how it might be halted. J Alzheimers Dis. 2016;54(4):1273–81.

    CAS  PubMed  Google Scholar 

  24. Hemling N, Roytta M, Rinne J, Pollanen P, Broberg E, Tapio V, et al. Herpesviruses in brains in Alzheimer’s and Parkinson’s diseases. Ann Neurol. 2003;54(2):267–71.

    CAS  PubMed  Google Scholar 

  25. Marques AR, Straus SE, Fahle G, Weir S, Csako G, Fischer SH. Lack of association between HSV-1 DNA in the brain, Alzheimer’s disease and apolipoprotein E4. J Neuro-Oncol. 2001;7(1):82–3.

    CAS  Google Scholar 

  26. Pisa D, Alonso R, Fernandez-Fernandez AM, Rabano A, Carrasco L. Polymicrobial infections in brain tissue from Alzheimer's disease patients. Sci Rep. 2017;7(1):5559.

    PubMed  PubMed Central  Google Scholar 

  27. Pisa D, Alonso R, Marina AI, Rabano A, Carrasco L. Human and microbial proteins from corpora amylacea of Alzheimer’s disease. Sci Rep. 2018;8(1):9880.

    PubMed  PubMed Central  Google Scholar 

  28. Pisa D, Alonso R, Rabano A, Rodal I, Carrasco L. Different brain regions are infected with fungi in Alzheimer’s disease. Sci Rep. 2015;5:15015.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Balin BJ, Little CS, Hammond CJ, Appelt DM, Whittum-Hudson JA, Gerard HC, et al. Chlamydophila pneumoniae and the etiology of late-onset Alzheimer’s disease. J Alzheimers Dis. 2008;13(4):371–80.

    CAS  PubMed  Google Scholar 

  30. Miklossy J. Emerging roles of pathogens in Alzheimer disease. Expert Rev Mol Med. 2011;13:e30.

    PubMed  Google Scholar 

  31. Gieffers J, Reusche E, Solbach W, Maass M. Failure to detect chlamydia pneumoniae in brain sections of Alzheimer’s disease patients. J Clin Microbiol. 2000;38(2):881–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Ring RH, Lyons JM. Failure to detect chlamydia pneumoniae in the late-onset Alzheimer’s brain. J Clin Microbiol. 2000;38(7):2591–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Alonso R, Pisa D, Fernandez-Fernandez AM, Carrasco L. Infection of fungi and bacteria in brain tissue from elderly persons and patients with Alzheimer’s disease. Front Aging Neurosci. 2018;10:159.

    PubMed  PubMed Central  Google Scholar 

  34. • Emery DC, Shoemark DK, Batstone TE, Waterfall CM, Coghill JA, Cerajewska TL, et al. 16S rRNA next generation sequencing analysis shows bacteria in Alzheimer's post-mortem brain. Front Aging Neurosci. 2017;9:195 This work represented an attempt to identify all the bacterial species present in AD brains using next generation sequencing-.

    PubMed  PubMed Central  Google Scholar 

  35. Carrasco L, Alonso R, Pisa D, Rabano A. Alzheimer’s disease and fungal infection. In: Miklossy J, editor. Handbook of Infection and Alzheimer’s Disease. 52017. p. 281–94.

  36. Alonso R, Pisa D, Marina AI, Morato E, Rabano A, Carrasco L. Fungal infection in patients with Alzheimer’s disease. J Alzheimers Dis. 2014;41(1):301–11.

    CAS  PubMed  Google Scholar 

  37. Alonso R, Pisa D, Marina AI, Morato E, Rabano A, Rodal I, et al. Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis. Int J Biol Sci. 2015;11(5):546–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Pisa D, Alonso R, Juarranz A, Rabano A, Carrasco L. Direct visualization of fungal infection in brains from patients with Alzheimer’s disease. J Alzheimers Dis. 2015;43(2):613–24.

    CAS  PubMed  Google Scholar 

  39. Pisa D, Alonso R, Rabano A, Horst MN, Carrasco L. Fungal enolase, beta-tubulin, and chitin are detected in brain tissue from Alzheimer’s disease patients. Front Microbiol. 2016;7:1772.

    PubMed  PubMed Central  Google Scholar 

  40. Alonso R, Pisa D, Rabano A, Carrasco L. Alzheimer’s disease and disseminated mycoses. Eur J Clin Microbiol Infect Dis. 2014;33(7):1125–32.

    CAS  PubMed  Google Scholar 

  41. Alonso R, Pisa D, Aguado B, Carrasco L. Identification of fungal species in brain tissue from Alzheimer’s disease by next-generation sequencing. J Alzheimers Dis. 2017;58(1):55–67.

    CAS  PubMed  Google Scholar 

  42. Parady B. Innate immune and fungal model of Alzheimer's disease. J Alzheimers Dis Rep. 2018;2(1):139–52.

    PubMed  PubMed Central  Google Scholar 

  43. Keller JN. Age-related neuropathology, cognitive decline, and Alzheimer’s disease. Ageing Res Rev. 2006;5(1):1–13.

    CAS  PubMed  Google Scholar 

  44. Song W, Zukor H, Liberman A, Kaduri S, Arvanitakis Z, Bennett DA, et al. Astroglial heme oxygenase-1 and the origin of corpora amylacea in aging and degenerating neural tissues. Exp Neurol. 2014;254:78–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Nishimura A, Ikemoto K, Satoh K, Yamamoto Y, Rand S, Brinkmann B, et al. The carbohydrate deposits detected by histochemical methods in the molecular layer of the dentate gyrus in the hippocampal formation of patients with schizophrenia, Down’s syndrome and dementia, and aged person. Glycoconj J. 2000;17(11):815–22.

    CAS  PubMed  Google Scholar 

  46. Pisa D, Alonso R, Rabano A, Carrasco L. Corpora Amylacea of brain tissue from neurodegenerative diseases are stained with specific antifungal antibodies. Front Neurosci. 2016;10:86.

    PubMed  PubMed Central  Google Scholar 

  47. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013.

    PubMed  Google Scholar 

  48. Aldridge GM, Birnschein A, Denburg NL, Narayanan NS. Parkinson’s disease dementia and dementia with Lewy bodies have similar neuropsychological profiles. Front Neurol. 2018;9:123.

    PubMed  PubMed Central  Google Scholar 

  49. Hall JM, Lewis SJG. Neural correlates of cognitive impairment in Parkinson’s disease: a review of structural MRI findings. Int Rev Neurobiol. 2019;144:1–28.

    PubMed  Google Scholar 

  50. Rey NL, Wesson DW, Brundin P. The olfactory bulb as the entry site for prion-like propagation in neurodegenerative diseases. Neurobiol Dis. 2018;109(Pt B):226–48.

    CAS  PubMed  Google Scholar 

  51. Boyko AA, Troyanova NI, Kovalenko EI, Sapozhnikov AM. Similarity and differences in inflammation-related characteristics of the peripheral immune system of patients with Parkinson’s and Alzheimer’s diseases. Int J Mol Sci. 2017;18(12).

  52. Troncoso-Escudero P, Parra A, Nassif M, Vidal RL. Outside in: unraveling the role of neuroinflammation in the progression of Parkinson’s disease. Front Neurol. 2018;9:860.

    PubMed  PubMed Central  Google Scholar 

  53. Heiss CN, Olofsson LE. The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system. J Neuroendocrinol. 2019;e12684.

    PubMed  Google Scholar 

  54. Kohler CA, Maes M, Slyepchenko A, Berk M, Solmi M, Lanctot KL, et al. The gut-brain axis, including the microbiome, leaky gut and bacterial translocation: mechanisms and pathophysiological role in Alzheimer’s disease. Curr Pharm Des. 2016;22(40):6152–66.

    CAS  PubMed  Google Scholar 

  55. Broxmeyer L. Parkinson’s: another look. Med Hypotheses. 2002;59(4):373–7.

    CAS  PubMed  Google Scholar 

  56. De Chiara G, Marcocci ME, Sgarbanti R, Civitelli L, Ripoli C, Piacentini R, et al. Infectious agents and neurodegeneration. Mol Neurobiol. 2012;46(3):614–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Vlajinac H, Dzoljic E, Maksimovic J, Marinkovic J, Sipetic S, Kostic V. Infections as a risk factor for Parkinson’s disease: a case-control study. Int J Neurosci. 2013;123(5):329–32.

    PubMed  Google Scholar 

  58. Berstad K, Berstad JER. Parkinson's disease; the hibernating spore hypothesis. Med Hypotheses. 2017;104:48–53.

    CAS  PubMed  Google Scholar 

  59. Sava V, Reunova O, Velasquez A, Sanchez-Ramos J. Can low level exposure to ochratoxin-A cause parkinsonism? J Neurol Sci. 2006;249(1):68–75.

    CAS  PubMed  Google Scholar 

  60. Pisa D, Alonso R, Carrasco L. Parkinson’s disease: a comprehensive analysis of fungi and bacteria in brain tissue. Int J Biol Sci. 2020;16:1135–52. https://doi.org/10.7150/ijbs.42257.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Oskarsson B, Gendron TF, Staff NP. Amyotrophic lateral sclerosis: an update for 2018. Mayo Clin Proc. 2018;93(11):1617–28.

    PubMed  Google Scholar 

  62. Iguchi Y, Katsuno M, Ikenaka K, Ishigaki S, Sobue G. Amyotrophic lateral sclerosis: an update on recent genetic insights. J Neurol. 2013;260(11):2917–27.

    CAS  PubMed  Google Scholar 

  63. Saberi S, Stauffer JE, Schulte DJ, Ravits J. Neuropathology of amyotrophic lateral sclerosis and its variants. Neurol Clin. 2015;33(4):855–76.

    PubMed  PubMed Central  Google Scholar 

  64. Huynh W, Simon NG, Grosskreutz J, Turner MR, Vucic S, Kiernan MC. Assessment of the upper motor neuron in amyotrophic lateral sclerosis. Clin Neurophysiol. 2016;127(7):2643–60.

    PubMed  Google Scholar 

  65. Corcia P, Couratier P, Blasco H, Andres CR, Beltran S, Meininger V, et al. Genetics of amyotrophic lateral sclerosis. Rev Neurol (Paris). 2017;173(5):254–62.

    CAS  Google Scholar 

  66. Renton AE, Chio A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014;17(1):17–23.

    CAS  PubMed  Google Scholar 

  67. • Castanedo-Vazquez D, Bosque-Varela P, Sainz-Pelayo A, Riancho J. Infectious agents and amyotrophic lateral sclerosis: another piece of the puzzle of motor neuron degeneration. J Neurol. 2019;266(1):27–36 This work analyzes a number of environmental conditions as potential risk factors in ALS. Also, studies about the involvement of microorganisms in ALS have been revised.

    CAS  PubMed  Google Scholar 

  68. Pagliardini V, Pagliardini S, Corrado L, Lucenti A, Panigati L, Bersano E, et al. Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: a survey clinic-based study. J Neurol Sci. 2015;348(1–2):245–50.

    CAS  PubMed  Google Scholar 

  69. Varghese AM, Sharma A, Mishra P, Vijayalakshmi K, Harsha HC, Sathyaprabha TN, et al. Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis. Clin Proteomics. 2013;10(1):19.

    PubMed  PubMed Central  Google Scholar 

  70. Alonso R, Pisa D, Fernandez-Fernandez AM, Rabano A, Carrasco L. Fungal infection in neural tissue of patients with amyotrophic lateral sclerosis. Neurobiol Dis. 2017;108:249–60.

    CAS  PubMed  Google Scholar 

  71. Alonso R, Pisa D, Carrasco L. Searching for bacteria in neural tissue from amyotrophic lateral sclerosis. Front Neurosci. 2019;13:171.

    PubMed  PubMed Central  Google Scholar 

  72. Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018;378(2):169–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Lassmann H. Mechanisms of neurodegeneration shared between multiple sclerosis and Alzheimer’s disease. J Neural Transm (Vienna). 2011;118(5):747–52.

    CAS  Google Scholar 

  74. Kawachi I, Lassmann H. Neurodegeneration in multiple sclerosis and neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2017;88(2):137–45.

    PubMed  Google Scholar 

  75. Ascherio A, Munger KL. Epidemiology of multiple sclerosis: from risk factors to prevention-an update. Semin Neurol. 2016;36(2):103–14.

    PubMed  Google Scholar 

  76. Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015;14(2):183–93.

    CAS  PubMed  Google Scholar 

  77. Dendrou CA, Fugger L. Immunomodulation in multiple sclerosis: promises and pitfalls. Curr Opin Immunol. 2017;49:37–43.

    CAS  PubMed  Google Scholar 

  78. Libbey JE, Cusick MF, Fujinami RS. Role of pathogens in multiple sclerosis. Int Rev Immunol. 2014;33(4):266–83.

    CAS  PubMed  Google Scholar 

  79. Laurence M, Benito-Leon J. Epstein-Barr virus and multiple sclerosis: updating Pender’s hypothesis. Mult Scler Relat Disord. 2017;16:8–14.

    PubMed  Google Scholar 

  80. Pormohammad A, Azimi T, Falah F, Faghihloo E. Relationship of human herpes virus 6 and multiple sclerosis: a systematic review and meta-analysis. J Cell Physiol. 2018;233(4):2850–62.

    CAS  PubMed  Google Scholar 

  81. Branton WG, Lu JQ, Surette MG, Holt RA, Lind J, Laman JD, et al. Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis. Sci Rep. 2016;6:37344.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Schrijver IA, van Meurs M, Melief MJ, Wim Ang C, Buljevac D, Ravid R, et al. Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis. Brain. 2001;124(Pt 8):1544–54.

    CAS  PubMed  Google Scholar 

  83. Benito-Leon J, Laurence M. The role of fungi in the etiology of multiple sclerosis. Front Neurol. 2017;8:535.

    PubMed  PubMed Central  Google Scholar 

  84. Benito-Leon J, Pisa D, Alonso R, Calleja P, Diaz-Sanchez M, Carrasco L. Association between multiple sclerosis and Candida species: evidence from a case-control study. Eur J Clin Microbiol Infect Dis. 2010;29(9):1139–45.

    CAS  PubMed  Google Scholar 

  85. Pisa D, Alonso R, Jimenez-Jimenez FJ, Carrasco L. Fungal infection in cerebrospinal fluid from some patients with multiple sclerosis. Eur J Clin Microbiol Infect Dis. 2013;32(6):795–801.

    CAS  PubMed  Google Scholar 

  86. Ramos M, Pisa D, Molina S, Rábano A, Juarranz A, Carrasco L. Fungal infection in patients with multiple sclerosis. Open Mycol J. 2008;2:22–8.

    CAS  Google Scholar 

  87. Saroukolaei SA, Ghabaee M, Shokri H, Badiei A, Ghourchian S. The role of Candida albicans in the severity of multiple sclerosis. Mycoses. 2016;59(11):697–704.

    CAS  PubMed  Google Scholar 

  88. Mollgaard M, Degn M, Sellebjerg F, Frederiksen JL, Modvig S. Cerebrospinal fluid chitinase-3-like 2 and chitotriosidase are potential prognostic biomarkers in early multiple sclerosis. Eur J Neurol. 2016;23(5):898–905.

    CAS  PubMed  Google Scholar 

  89. Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, Malmestrom C, et al. Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis. J Neurochem. 2017;141(2):296–304.

    CAS  PubMed  Google Scholar 

  90. Basketter DA, White IR, Burleson FG, Burleson GR, Kimber I. Dimethylfumarate: potency prediction and clinical experience. Contact Dermatitis. 2013;68(5):269–72.

    CAS  PubMed  Google Scholar 

  91. Hamidi V, Couto E, Ringerike T, Klemp M. A multiple treatment comparison of eleven disease-modifying drugs used for multiple sclerosis. J Clin Med Res. 2018;10(2):88–105.

    PubMed  Google Scholar 

  92. Alonso R, Fernandez-Fernandez AM, Pisa D, Carrasco L. Multiple sclerosis and mixed microbial infections. Direct identification of fungi and bacteria in nervous tissue. Neurobiol Dis. 2018;117:42–61.

    CAS  PubMed  Google Scholar 

  93. Testa CM, Jankovic J. Huntington disease: a quarter century of progress since the gene discovery. J Neurol Sci. 2019;396:52–68.

    CAS  PubMed  Google Scholar 

  94. Caron NS, Wright GEB, Hayden MR. Huntington Disease. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al., editors. GeneReviews((R)). Seattle (WA)1993–2019. 1998.

  95. Waldvogel HJ, Kim EH, Tippett LJ, Vonsattel JP, Faull RL. The neuropathology of Huntington’s disease. Curr Top Behav Neurosci. 2015;22:33–80.

    CAS  PubMed  Google Scholar 

  96. Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983;306(5940):234–8.

    CAS  PubMed  Google Scholar 

  97. MacDonald ME, Ambrose CM, Duyao MP, Myers R, Lin C. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72(6):971–83.

    Google Scholar 

  98. Holmans PA, Massey TH, Jones L. Genetic modifiers of Mendelian disease: Huntington’s disease and the trinucleotide repeat disorders. Hum Mol Genet. 2017;26(R2):R83–90.

    CAS  PubMed  Google Scholar 

  99. Dickey AS, La Spada AR. Therapy development in Huntington disease: from current strategies to emerging opportunities. Am J Med Genet A. 2018;176(4):842–61.

    CAS  PubMed  Google Scholar 

  100. Saudou F, Humbert S. The biology of Huntingtin. Neuron. 2016;89(5):910–26.

    CAS  PubMed  Google Scholar 

  101. Alonso R, Pisa D, Carrasco L. Brain microbiota in Huntington’s disease patient. Front Microbiol. 2019;10:2622.

    PubMed  PubMed Central  Google Scholar 

  102. Ala TA, Doss RC, Sullivan CJ. Reversible dementia: a case of cryptococcal meningitis masquerading as Alzheimer's disease. J Alzheimers Dis. 2004;6:503–8.

    PubMed  Google Scholar 

  103. Hoffmann M, Muniz J, Carroll E, De Villasante J. Cryptococcal meningitis misdiagnosed as Alzheimer’s disease: complete neurological and cognitive recovery with treatment. J Alzheimers Dis. 2009;16:517–20.

    PubMed  Google Scholar 

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We acknowledge an institutional grant from Centro de Biología Molecular “Severo Ochoa” from the Fundación Ramón Areces and Banco de Santander.

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Carrasco, L., Pisa, D. & Alonso, R. Polymicrobial Infections and Neurodegenerative Diseases. Curr Clin Micro Rpt 7, 20–30 (2020). https://doi.org/10.1007/s40588-020-00139-3

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