333
Views
0
CrossRef citations to date
0
Altmetric
Perspective

Viruses - a major cause of amyloid deposition in the brain

ORCID Icon, , ORCID Icon, , , , , , , , , , & ORCID Icon show all
Pages 775-790 | Received 01 Apr 2023, Accepted 31 Jul 2023, Published online: 09 Aug 2023

References

  • Alzheimer A. Über eine eigenartige Erkrankung der hirnrinde. Allg Z Psychiatr Psychisch Gerichtl Med. 1907;64:146–148.
  • Lanoiselée HM, Nicolas G, Wallon D, et al. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLOS Med. 2017 Mar 28;14(3):e1002270. doi: 10.1371/journal.pmed.1002270
  • Goedert M. Oskar Fischer and the study of dementia. Brain. 2009 Apr;132(Pt 4):1102–1111. doi: 10.1093/brain/awn256
  • Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci. 1991 Oct;12(10):383–388. doi: 10.1016/0165-6147(91)90609-V
  • Beyreuther K, Masters CL. Amyloid precursor protein (APP) and beta A4 amyloid in the etiology of Alzheimer’s disease: precursor-product relationships in the derangement of neuronal function. Brain Pathol. 1991 Jul;1(4):241–251. doi: 10.1111/j.1750-3639.1991.tb00667.x
  • Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016 Jun 1;8(6):595–608. doi: 10.15252/emmm.201606210
  • Capell A, Steiner H, Willem M, et al. Maturation and pro-peptide cleavage of beta-secretase. J Biol Chem. 2000 Oct 6;275(40):30849–30854. doi: 10.1074/jbc.M003202200
  • Cunningham C. Microglia and neurodegeneration: the role of systemic inflammation. Glia. 2013 Jan;61(1):71–90. doi: 10.1002/glia.22350
  • Mosher KI, Wyss-Coray T. Microglial dysfunction in brain aging and Alzheimer’s disease. Biochem Pharmacol. 2014 Apr 15;88(4):594–604. doi: 10.1016/j.bcp.2014.01.008
  • Mecca C, Giambanco I, Donato R, et al. Microglia and aging: the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes. Int J Mol Sci. 2018 Jan 22;19(1):318. doi: 10.3390/ijms19010318
  • Krasemann S, Madore C, Cialic R, et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity. 2017 Sep 19;47(3):566–581.e9. doi: 10.1016/j.immuni.2017.08.008
  • Niraula A, Sheridan JF, Godbout JP. Microglia priming with aging and stress. Neuropsychopharmacology. 2017 Jan;42(1):318–333. doi: 10.1038/npp.2016.185
  • Rangaraju S, Dammer EB, Raza SA, et al. Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer’s disease. Mol Neurodegener. 2018 May 21;13(1):24. doi: 10.1186/s13024-018-0254-8.
  • Dionisio-Santos DA, Olschowka JA, O’Banion MK. Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease. J Neuroinflammation. 2019 Apr 5;16(1):74. doi: 10.1186/s12974-019-1453-0.
  • Ciarlo E, Heinonen T, Théroude C, et al. Trained immunity confers broad-spectrum protection against bacterial infections. J Infect Dis. 2020 Nov 9;222(11):1869–1881. doi: 10.1093/infdis/jiz692
  • Rentz DM, Locascio JJ, Becker JA, et al. Cognition, reserve, and amyloid deposition in normal aging. Ann Neurol. 2010 Mar;67(3):353–364. doi: 10.1002/ana.21904
  • Webers A, Heneka MT, Gleeson PA. The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of alzheimer’s disease. Immunol Cell Biol. 2020 Jan;98(1):28–41. doi: 10.1111/imcb.12301
  • Walker KA, Gottesman RF, Wu A, et al. Systemic inflammation during midlife and cognitive change over 20 years: the ARIC study. Neurology. 2019 Mar 12;92(11):e1256–e1267. doi: 10.1212/WNL.0000000000007094.
  • Schmidt R, Schmidt H, Curb JD, et al. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia aging study. Ann Neurol. 2002 Aug;52(2):168–174. doi: 10.1002/ana.10265
  • Bourgade K, Le Page A, Bocti C, et al. Protective effect of amyloid-β peptides against herpes simplex virus-1 infection in a neuronal cell culture model. J Alzheimers Dis. 2016;50(4):1227–1241. doi: 10.3233/JAD-150652.
  • Cuddy SR, Cliffe AR, Tarakanova VL. The intersection of innate immune pathways with the latent herpes simplex virus genome. J Virol. 2023 May 31;97(5):e0135222. doi: 10.1128/jvi.01352-22
  • Chen S, Liao Z, Xu P. Mitochondrial control of innate immune responses. Front Immunol. 2023 May 30;14:1166214. doi: 10.3389/fimmu.2023.1166214
  • Aarreberg LD, Esser-Nobis K, Driscoll C, et al. Interleukin-1β induces mtDNA release to activate innate immune signaling via Cgas-STING. Mol Cell. 2019 May 16;74(4):801–815.e6. doi: 10.1016/j.molcel.2019.02.038
  • Roy ER, Wang B, Wan YW, et al. Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease. J Clin Invest. 2020 Apr 1;130(4):1912–1930. doi: 10.1172/JCI133737.
  • Roy ER, Chiu G, Li S, et al. Concerted type I interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid β plaques. Immunity. 2022 May 10;55(5):879–894.e6. doi: 10.1016/j.immuni.2022.03.018
  • Mehta D, Jackson R, Paul G, et al. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin Investig Drugs. 2017 Jun;26(6):735–739. doi: 10.1080/13543784.2017.1323868
  • Vaz M, Silvestre S. Alzheimer’s disease: recent treatment strategies. Eur J Pharmacol. 2020 Nov 15;887:173554. doi: 10.1016/j.ejphar.2020.173554
  • Salloway S, Chalkias S, Barkhof F, et al. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol. 2022 Jan 1;79(1):13–21. doi: 10.1001/jamaneurol.2021.4161
  • Lee EY, Srinivasan Y, de Anda J, et al. Functional reciprocity of amyloids and antimicrobial peptides: rethinking the role of supramolecular assembly in host defense, immune activation, and inflammation. Front Immunol. 2020 Jul 31;11:1629. doi: 10.3389/fimmu.2020.01629
  • Hammer ND, Wang X, McGuffie BA, et al. Amyloids: friend or foe? J Alzheimers Dis. 2008 May;13(4):407–419. doi: 10.3233/JAD-2008-13406
  • Shanmugam N, MODG B, Sanz-Hernandez M, et al. Herpes simplex virus encoded ICP6 protein forms functional amyloid assemblies with necroptosis-associated host proteins. Biophys Chem. 2021 Feb;269:106524. doi: 10.1016/j.bpc.2020.106524
  • Soscia SJ, Kirby JE, Washicosky KJ, et al. The alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One. 2010 Mar 3;5(3):e9505. doi: 10.1371/journal.pone.0009505.
  • Jeong H, Shin H, Hong S, et al. Physiological roles of monomeric amyloid-β and implications for Alzheimer’s disease therapeutics. Exp Neurobiol. 2022 Apr 30;31(2):65–88. doi: 10.5607/en22004
  • Snowdon DA, Greiner LH, Mortimer JA, et al. Brain infarction and the clinical expression of Alzheimer disease. The nun study. JAMA. 1997 Mar 12;277(10):813–817. doi: 10.1001/jama.1997.03540340047031.
  • Nordestgaard LT, Christoffersen M, Frikke-Schmidt R. Shared risk factors between dementia and atherosclerotic cardiovascular disease. Int J Mol Sci. 2022 Aug 29;23(17):9777. doi: 10.3390/ijms23179777.
  • Rajendran L, Honsho M, Zahn TR, et al. Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11172–11177. doi: 10.1073/pnas.0603838103
  • Fulop T, Witkowski JM, Bourgade K, et al. Can an infection hypothesis explain the beta amyloid hypothesis of Alzheimer’s disease? Front Aging Neurosci. 2018 Jul 24;10:224. doi: 10.3389/fnagi.2018.00224.
  • Itzhaki RF, Lin WR, Shang D, et al. Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet. 1997 Jan 25;349(9047):241–244. doi: 10.1016/S0140-6736(96)10149-5
  • Jamieson GA, Maitland NJ, Wilcock GK, et al. Latent herpes simplex virus type 1 in normal and Alzheimer’s disease brains. J Med Virol. 1991 Apr;33(4):224–227. doi: 10.1002/jmv.1890330403
  • Wozniak MA, Mee AP, Itzhaki RF. Herpes simplex virus type 1 DNA is located within Alzheimer’s disease amyloid plaques. J Pathol. 2009 Jan;217(1):131–138. doi: 10.1002/path.2449.
  • Miklossy J. Bacterial amyloid and DNA are important constituents of senile plaques: further evidence of the spirochetal and biofilm nature of senile plaques. J Alzheimers Dis. 2016 Jun 13;53(4):1459–1473. doi: 10.3233/JAD-160451.
  • Balin BJ, Hammond CJ, Little CS, et al. Chlamydia pneumoniae: an etiologic agent for late-onset dementia. Front Aging Neurosci. 2018 Oct 9;10:302. doi: 10.3389/fnagi.2018.00302
  • Dioguardi M, Crincoli V, Laino L, et al. The role of periodontitis and periodontal bacteria in the onset and progression of Alzheimer’s disease: A systematic review. J Clin Med. 2020 Feb 11;9(2):495. doi: 10.3390/jcm9020495
  • White MR, Kandel R, Tripathi S, et al. Alzheimer’s associated beta-amyloid protein inhibits influenza a virus and modulates viral interactions with phagocytes. PLoS One. 2014 Jul 2;9(7):e101364. doi: 10.1371/journal.pone.0101364
  • Talapko J, Meštrović T, Juzbašić M, et al. Antimicrobial peptides-mechanisms of action, antimicrobial effects and clinical applications. Antibiotics. 2022 Oct 16;11(10):1417. doi: 10.3390/antibiotics11101417
  • Eimer WA, Vijaya Kumar DK, Navalpur Shanmugam NK, et al. Alzheimer’s disease-associated β-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron. 2018 Jul 11;99(1):56–63.e3. doi: 10.1016/j.neuron.2018.06.030
  • Kumar DK, Choi SH, Washicosky KJ, et al. Amyloid-β peptide protects against microbial infection in mouse and worm models of alzheimer’s disease. Sci Transl Med. 2016 May 25;8(340):340ra72. doi: 10.1126/scitranslmed.aaf1059
  • Bishop GM, Robinson SR. The amyloid hypothesis: let sleeping dogmas lie? Neurobiol Aging. 2002 Nov;23(6):1101–1105. doi: 10.1016/S0197-4580(02)00050-7
  • Wozniak MA, Itzhaki RF, Shipley SJ, et al. Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Neurosci Lett. 2007 Dec 18;429(2–3):95–100. doi: 10.1016/j.neulet.2007.09.077
  • Ní Chasaide C, Lynch MS. The role of the immune system in driving neuroinflammation. Brain Neurosci Adv. 2020 Jan 29;4:2398212819901082. doi: 10.1177/2398212819901082
  • Hur JY, Frost GR, Wu X, et al. The innate immunity protein IFITM3 modulates γ-secretase in alzheimer’s disease. Nature. 2020 Oct;586(7831):735–740.
  • Zheng K, Liu Q, Wang S, et al. HSV-1-encoded microRNA miR-H1 targets Ubr1 to promote accumulation of neurodegeneration-associated protein. Virus Genes. 2018 Jun;54(3):343–350. doi: 10.1007/s11262-018-1551-6
  • Butler L, Walker KA. The role of chronic infection in Alzheimer’s disease: instigators, co-conspirators, or bystanders? Curr Clin Microbiol Rep. 2021 Dec;8(4):199–212. doi: 10.1007/s40588-021-00168-6
  • Readhead B, Haure-Mirande JV, Funk CC, et al. Multiscale analysis of independent Alzheimer’s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron. 2018 Jul 11;99(1):64–82.e7. doi: 10.1016/j.neuron.2018.05.023
  • Nicoll MP, Proença JT, Efstathiou S. The molecular basis of herpes simplex virus latency. FEMS Microbiol Rev. 2012 May;36(3):684–705. doi: 10.1111/j.1574-6976.2011.00320.x
  • Grinde B. Herpesviruses: latency and reactivation – viral strategies and host response. J Oral Microbiol. 2013 Oct 25;5(1):22766. doi: 10.3402/jom.v5i0.22766
  • Aiello AE, Haan M, Blythe L, et al. The influence of latent viral infection on rate of cognitive decline over 4 years. J Am Geriatr Soc. 2006 Jul;54(7):1046–1054. doi: 10.1111/j.1532-5415.2006.00796.x
  • Baringer JR, Swoveland P. Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med. 1973 Mar 29;288(13):648–650. doi: 10.1056/NEJM197303292881303
  • Malkin JE, Morand P, Malvy D, et al. Seroprevalence of HSV-1 and HSV-2 infection in the general French population. Sex Transm Infect. 2002 Jun;78(3):201–203. doi: 10.1136/sti.78.3.201
  • Bourgade K, Dupuis G, Frost EH, et al. Anti-viral properties of amyloid-β peptides. J Alzheimers Dis. 2016 Oct 4;54(3):859–878. doi: 10.3233/JAD-160517
  • De Chiara G, Piacentini R, Fabiani M, et al. Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice. PLOS Pathog. 2019 Mar 14;15(3):e1007617. doi: 10.1371/journal.ppat.1007617
  • Fülöp T, Itzhaki RF, Balin BJ, et al. Role of microbes in the development of alzheimer’s disease: state of the art - an international symposium presented at the 2017 IAGG congress in san francisco. Front Genet. 2018 Sep 10;9:362. doi: 10.3389/fgene.2018.00362
  • He Q, Liu H, Huang C, et al. Herpes simplex virus 1-induced blood-brain barrier damage involves apoptosis associated with GM130-mediated golgi stress. Front Mol Neurosci. 2020 Jan 24;13:2. doi: 10.3389/fnmol.2020.00002
  • Bourgade K, Garneau H, Giroux G, et al. β-amyloid peptides display protective activity against the human Alzheimer’s disease-associated herpes simplex virus-1. Biogerontology. 2015 Feb;16(1):85–98. doi: 10.1007/s10522-014-9538-8
  • Ezzat K, Pernemalm M, Pålsson S, et al. The viral protein corona directs viral pathogenesis and amyloid aggregation. Nat Commun. 2019 May 27;10(1):2331. doi: 10.1038/s41467-019-10192-2
  • Leblanc P, Vorberg IM, Haigh CL. Viruses in neurodegenerative diseases: more than just suspects in crimes. PLOS Pathog. 2022 Aug 4;18(8):e1010670. doi: 10.1371/journal.ppat.1010670
  • Wozniak MA, Frost AL, Itzhaki RF. Alzheimer’s disease-specific tau phosphorylation is induced by herpes simplex virus type 1. J Alzheimers Dis. 2009;16(2):341–350. doi: 10.3233/JAD-2009-0963
  • Piacentini R, Civitelli L, Ripoli C, et al. HSV-1 promotes ca2+ -mediated APP phosphorylation and Aβ accumulation in rat cortical neurons. Neurobiol Aging. 2011 Dec;32(12):2323.e13–26. doi: 10.1016/j.neurobiolaging.2010.06.009
  • Itzhaki RF, Wozniak MA. Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in alzheimer’s disease and other disorders. Prog Lipid Res. 2006 Jan;45(1):73–90. doi: 10.1016/j.plipres.2005.11.003
  • Lövheim H, Norman T, Weidung B, et al. Herpes simplex virus, aPOEɛ4, and cognitive decline in old age: results from the Betula cohort study. J Alzheimers Dis. 2019;67(1):211–220. doi: 10.3233/JAD-171162
  • Lopatko Lindman K, Weidung B, Olsson J, et al. A genetic signature including apolipoprotein Eε4 potentiates the risk of herpes simplex-associated alzheimer’s disease. Alzheimers Dement (N Y). 2019 Nov 4;5:697–704. doi: 10.1016/j.trci.2019.09.014
  • Irizarry MC, Deng A, Lleo A, et al. Apolipoprotein E modulates gamma-secretase cleavage of the amyloid precursor protein. J Neurochem. 2004 Sep;90(5):1132–1143. doi: 10.1111/j.1471-4159.2004.02581.x
  • Nemergut M, Batkova T, Vigasova D, et al. Increased occurrence of Treponema spp. and double-species infections in patients with Alzheimer’s disease. Sci Total Environ. 2022 Oct 20;844:157114. doi: 10.1016/j.scitotenv.2022.157114
  • Lehrer S, Rheinstein PH. Vaccination reduces risk of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Discov Med. 2022 Sep;34(172):97–101.
  • Levine KS, Leonard HL, Blauwendraat C, et al. Virus exposure and neurodegenerative disease risk across national biobanks. Neuron. 2023 Jan 11;111(7):1086–1093.e2. doi: 10.1016/j.neuron.2022.12.029
  • Cocoros NM, Svensson E, Szépligeti SK, et al. Long-term risk of Parkinson disease following influenza and other infections. JAMA Neurol. 2021 Dec 1;78(12):1461–1470. doi: 10.1001/jamaneurol.2021.3895
  • Allnutt MA, Johnson K, Bennett DA, et al. Human herpesvirus 6 detection in Alzheimer’s disease cases and controls across multiple cohorts. Neuron. 2020 Mar 18;105(6):1027–1035.e2. doi: 10.1016/j.neuron.2019.12.031.
  • Carbone I, Lazzarotto T, Ianni M, et al. Herpes virus in alzheimer’s disease: relation to progression of the disease. Neurobiol Aging. 2014 Jan;35(1):122–129. doi: 10.1016/j.neurobiolaging.2013.06.024
  • Stowe RP, Peek MK, Cutchin MP, et al. Reactivation of herpes simplex virus type 1 is associated with cytomegalovirus and age. J Med Virol. 2012 Nov;84(11):1797–1802. doi: 10.1002/jmv.23397
  • Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a007096. doi: 10.1101/cshperspect.a007096
  • Saylor D, Dickens AM, Sacktor N, et al. HIV-associated neurocognitive disorder - pathogenesis and prospects for treatment. Nat Rev Neurol. 2016 May;12(5):309. doi: 10.1038/nrneurol.2016.53
  • Kim J, Yoon JH, Kim YS, et al. HIV-1 tat interacts with and regulates the localization and processing of amyloid precursor protein. PLoS One. 2013 Nov 29;8(11):e77972. doi: 10.1371/journal.pone.0077972
  • Fulop T, Witkowski JM, Larbi A, et al. Does HIV infection contribute to increased beta-amyloid synthesis and plaque formation leading to neurodegeneration and Alzheimer’s disease? J Neurovirol. 2019 Oct;25(5):634–647. doi: 10.1007/s13365-019-00732-3
  • Rempel HC, Pulliam L. HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS. 2005 Jan 28;19(2):127–135. doi: 10.1097/00002030-200501280-00004
  • Damiano RF, Guedes BF, de Rocca CC, et al. Cognitive decline following acute viral infections: literature review and projections for post-COVID-19. Eur Arch Psychiatry Clin Neurosci. 2022 Feb;272(1):139–154.
  • Crunfli F, Carregari VC, Veras FP, et al. Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. Proc Natl Acad Sci U S A. 2022 Aug 30;119(35):e2200960119. doi: 10.1073/pnas.2200960119
  • Naughton SX, Raval U, Pasinetti GM. Potential novel role of COVID-19 in alzheimer’s disease and preventative mitigation strategies. J Alzheimers Dis. 2020;76(1):21–25. doi: 10.3233/JAD-200537
  • Kokkoris S, Stamataki E, Emmanouil G, et al. Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study. eNeurologicalsci. 2022 Dec;29:100434. doi: 10.1016/j.ensci.2022.100434
  • Cairns DM, Itzhaki RF, Kaplan DL. Potential involvement of varicella zoster virus in Alzheimer’s disease via reactivation of quiescent herpes simplex virus type 1. J Alzheimers Dis. 2022;88(3):1189–1200. doi: 10.3233/JAD-220287
  • de Erausquin GA, Snyder H, Brugha TS, et al. Chronic neuropsychiatric sequelae of SARS-CoV-2: protocol and methods from the Alzheimer’s association global consortium. Alzheimer’s Dement: Transl Res Clin. 2022 Sep 22;8(1):e12348. Alzheimers Dement (N Y). doi: 10.1002/trc2.12348
  • Kessing CF, Tyor WR. Interferon-α induces neurotoxicity through activation of the type I receptor and the GluN2A subunit of the NMDA receptor. J Interferon Cytokine Res. 2015 Apr;35(4):317–324. doi: 10.1089/jir.2014.0105
  • Thaney VE, Kaul M. Type I interferons in NeuroHIV. Viral Immunol. 2019 Jan;32(1):7–14. doi: 10.1089/vim.2018.0085
  • Vavougios GD, Nday C, Pelidou SH, et al. Outside-in induction of the IFITM3 trafficking system by infections, including SARS-CoV-2, in the pathobiology of Alzheimer’s disease. Brain Behav Immun Health. 2021 Jul;14:100243. doi: 10.1016/j.bbih.2021.100243
  • Nicholl MJ, Robinson LH, Preston CM. Activation of cellular interferon-responsive genes after infection of human cells with herpes simplex virus type 1. J Gen Virol. 2000 Sep;81(Pt 9):2215–2218. doi: 10.1099/0022-1317-81-9-2215
  • Cairns DM, Rouleau N, Parker RN, et al. A 3D human brain-like tissue model of herpes-induced Alzheimer’s disease. Sci Adv. 2020 May 6;6(19):eaay8828. doi: 10.1126/sciadv.aay8828
  • Orr ME, Oddo S. Autophagic/Lysosomal dysfunction in Alzheimer’s disease. Alzheimers Res Ther. 2013 Oct 29;5(5):53. doi: 10.1186/alzrt217
  • Vavougios GD, de Erausquin GA, Snyder HM. Type I interferon signaling in SARS-CoV-2 associated neurocognitive disorder (SAND): mapping host-virus interactions to an etiopathogenesis. Front Neurol. 2022 Dec 7;13:1063298. doi: 10.3389/fneur.2022.1063298
  • Moir RD, Lathe R, Tanzi RE. The antimicrobial protection hypothesis of Alzheimer’s disease. Alzheimers Dement. 2018 Dec;14(12):1602–1614. doi: 10.1016/j.jalz.2018.06.3040
  • Varesi A, Pierella E, Romeo M, et al. The potential role of gut microbiota in Alzheimer’s disease: from diagnosis to treatment. Nutrients. 2022 Feb 5;14(3):668. doi: 10.3390/nu14030668
  • Krishaa L, Ng TKS, Wee HN, et al. Gut-brain axis through the lens of gut microbiota and their relationships with Alzheimer’s disease pathology: review and recommendations. Mech Ageing Dev. 2023 Feb 1;211:111787. doi: 10.1016/j.mad.2023.111787
  • Cunnane SC, Courchesne-Loyer A, St-Pierre V, et al. Can ketones compensate for deteriorating brain glucose uptake during aging? implications for the risk and treatment of Alzheimer’s disease. Ann N Y Acad Sci. 2016 Mar;1367(1):12–20. doi: 10.1111/nyas.12999
  • Liu P, Wu L, Peng G, et al. Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort. Brain Behav Immun. 2019 Aug;80:633–643.
  • Cattaneo A, Cattane N, Galluzzi S, et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017 Jan;49:60–68.
  • Liccardo D, Marzano F, Carraturo F, et al. Potential bidirectional relationship between periodontitis and Alzheimer’s disease. Front Physiol. 2020 Jul 3;11:683. doi: 10.3389/fphys.2020.00683
  • Olsen I, Singhrao SK. Low levels of salivary lactoferrin may affect oral dysbiosis and contribute to Alzheimer’s disease: A hypothesis. Med Hypotheses. 2021 Jan;146:110393. doi: 10.1016/j.mehy.2020.110393
  • Tzeng NS, Chung CH, Lin FH, et al. Anti-herpetic medications and reduced risk of dementia in patients with herpes simplex virus infections-a nationwide, population-based cohort study in Taiwan. Neurotherapeutics. 2018 Apr;15(2):417–429. doi: 10.1007/s13311-018-0611-x
  • Linard M, Bezin J, Hucteau E, et al. Antiherpetic drugs: a potential way to prevent Alzheimer’s disease? Alzheimers Res Ther. 2022 Jan 7;14(1):3. doi: 10.1186/s13195-021-00950-0
  • Ali E, Shaikh A. Influenza vaccination and dementia risk; an unanticipated benefit? Ann Med Surg. 2022 Jul 19;80:104187. doi: 10.1016/j.amsu.2022.104187
  • Lehrer S, Rheinstein PH. Herpes zoster vaccination reduces risk of dementia. In Vivo. 2021 Nov;35(6):3271–3275. doi: 10.21873/invivo.12622
  • Lophatananon A, Mekli K, Cant R, et al. Zostavax vaccination and risk of developing dementia: a nested case-control study-results from the UK biobank cohort. BMJ Open. 2021 Oct 8;11(10):e045871. doi: 10.1136/bmjopen-2020-045871
  • Weinberg MS, Zafar A, Magdamo C, et al. Association of BCG vaccine treatment with death and dementia in patients with non-muscle-invasive bladder cancer. JAMA Netw Open. 2023 May 1;6(5):e2314336. doi: 10.1001/jamanetworkopen.2023.14336
  • Yadav JK. Structural and functional swapping of amyloidogenic and antimicrobial peptides: redefining the role of amyloidogenic propensity in disease and host defense. J Pept Sci. 2022 Apr;28(4):e3378. doi: 10.1002/psc.3378
  • Chen D, Liu X, Chen Y, et al. Amyloid peptides with antimicrobial and/or microbial agglutination activity. Appl Microbiol Biotechnol. 2022 Dec;106(23):7711–7720. doi: 10.1007/s00253-022-12246-w
  • van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023 Jan 5;388(1):9–21
  • Gonçalves CA, Bobermin LD, Sesterheim P, et al. SARS-CoV-2-induced amyloidgenesis: not one, but three hypotheses for cerebral COVID-19 outcomes. Metabolites. 2022 Nov 11;12(11):1099. doi: 10.3390/metabo12111099
  • Hsu JT, Tien CF, Yu GY, et al. The effects of Aβ1-42 binding to the SARS-CoV-2 spike protein S1 subunit and angiotensin-converting enzyme 2. Int J Mol Sci. 2021 Jul 30;22(15):8226. doi: 10.3390/ijms22158226
  • Ahmed SSSJ, Paramasivam P, Kamath M, et al. Genetic exchange of lung-derived exosome to brain causing neuronal changes on COVID-19 infection. Mol Neurobiol. 2021 Oct;58(10):5356–5368. doi: 10.1007/s12035-021-02485-9
  • Alexander MR, Brice AM, Jansen van Vuren P, et al. Ribosome-profiling reveals restricted post transcriptional expression of antiviral cytokines and transcription factors during SARS-CoV-2 infection. Int J Mol Sci. 2021 Mar 25;22(7):3392. doi: 10.3390/ijms22073392
  • Lam SM, Zhang C, Wang Z, et al. A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19. Nat Metab. 2021 Jul;3(7):909–922. doi: 10.1038/s42255-021-00425-4
  • Magusali N, Graham AC, Piers TM, et al. A genetic link between risk for alzheimer’s disease and severe COVID-19 outcomes via the OAS1 gene. Brain. 2021 Dec 31;144(12):3727–3741. doi: 10.1093/brain/awab337
  • Yang AC, Kern F, Losada PM, et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19. Nature. 2021 Jul;595(7868):565–571. doi: 10.1038/s41586-021-03710-0
  • Zhou Y, Xu J, Hou Y, et al. Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment. Alzheimers Res Ther. 2021 Jun 9;13(1):110. doi: 10.1186/s13195-021-00850-3
  • Shi G, Kenney AD, Kudryashova E, et al. Opposing activities of IFITM proteins in SARS-CoV-2 infection. Embo J. 2021 Feb 1;40(3):e106501. doi: 10.15252/embj.2020106501
  • Choi UY, Kang JS, Hwang YS, et al. Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases. Exp Mol Med. 2015 Mar 6;47(3):e144. doi: 10.1038/emm.2014.110
  • Mavrikaki M, Lee JD, Solomon IH, et al. Severe COVID-19 is associated with molecular signatures of aging in the human brain. Nat Aging. 2022 Dec;2(12):1130–1137. doi: 10.1038/s43587-022-00321-w
  • Vavougios GD, Mavridis T, Artemiadis A, et al. Trained immunity in viral infections, alzheimer’s disease and multiple sclerosis: A convergence in type I interferon signalling and IFNβ-1a. Biochim Biophys Acta Mol Basis Dis. 2022 Sep 1;1868(9):166430. doi: 10.1016/j.bbadis.2022.166430
  • Svensson A, Jäkärä E, Shestakov A, et al. Inhibition of γ-secretase cleavage in the notch signaling pathway blocks HSV-2-induced type I and type II interferon production. Viral Immunol. 2010 Dec;23(6):647–651. doi: 10.1089/vim.2010.0013
  • Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019 Jan 23;5(1):eaau3333. doi: 10.1126/sciadv.aau3333
  • Li L, Zhang X, Yang D, et al. Hypoxia increases abeta generation by altering beta- and gamma-cleavage of APP. Neurobiol Aging. 2009 Jul;30(7):1091–1098. doi: 10.1016/j.neurobiolaging.2007.10.011
  • Heavener KS, Bradshaw EM. The aging immune system in alzheimer’s and parkinson’s diseases. Semin Immunopathol. 2022 Sep;44(5):649–657. doi: 10.1007/s00281-022-00944-6
  • Lutshumba J, Nikolajczyk BS, Bachstetter AD. Dysregulation of systemic immunity in aging and dementia. Front Cell Neurosci. 2021 Jun 22;15:652111. doi: 10.3389/fncel.2021.652111
  • Nelson PT, Lee EB, Cykowski MD, et al. LATE-NC staging in routine neuropathologic diagnosis: an update. Acta Neuropathol. 2023 Feb;145(2):159–173. doi: 10.1007/s00401-022-02524-2
  • Nelson PT, Schneider JA, Jicha GA, et al. When Alzheimer’s is LATE: why does it matter? Annals Of Neurology. 2023 May 28;94(2):211–222. doi: 10.1002/ana.26711
  • Goldeck D, Witkowski JM, Fülop T, et al. Peripheral immune signatures in Alzheimer disease. Curr Alzheimer Res. 2016;13(7):739–749. doi: 10.2174/1567205013666160222112444
  • Le Page A, Dupuis G, Frost EH, et al. Role of the peripheral innate immune system in the development of Alzheimer’s disease. Exp Gerontol. 2018 Jul 1;107:59–66. doi: 10.1016/j.exger.2017.12.019
  • Yadav P, Lee YH, Panday H, et al. Implications of microorganisms in Alzheimer’s disease. Curr Issues Mol Biol. 2022 Sep 30;44(10):4584–4615. doi: 10.3390/cimb44100314
  • Fulop T, Tripathi S, Rodrigues S, et al. Targeting impaired antimicrobial immunity in the brain for the treatment of Alzheimer’s disease. Neuropsychiatr Dis Treat. 2021 May 4;17:1311–1339. doi: 10.2147/NDT.S264910
  • Toups K, Hathaway A, Gordon D, et al. Precision medicine approach to Alzheimer’s disease: successful pilot project. J Alzheimers Dis. 2022;88(4):1411–1421. doi: 10.3233/JAD-215707
  • Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255–2263. doi: 10.1016/S0140-6736(15)60461-5
  • Uwishema O, Mahmoud A, Sun J, et al. Is alzheimer’s disease an infectious neurological disease? A review of the literature. Brain Behav. 2022 Aug;12(8):e2728. doi: 10.1002/brb3.2728
  • Bocharova O, Pandit NP, Molesworth K, et al. Alzheimer’s disease-associated β-amyloid does not protect against herpes simplex virus 1 infection in the mouse brain. J Biol Chem. 2021 Jul;297(1):100845. doi: 10.1016/j.jbc.2021.100845

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.