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The Possibility of an Infectious Etiology of Alzheimer Disease

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Abstract

Over the past three decades, there has been constant postulation regarding the infectious etiology of Alzheimer disease (AD), which in turn suggests the vital role of various infectious agents in AD-associated inflammatory pathways. Recent findings indicate anti-microbial properties of Aβ, and suggest that Aβ production and deposition in AD might be induced by infectious agents. Several types of spirochetes have been associated to dementia, cortical atrophy, and pathological and biological hallmarks of AD. A significant association between AD spirochetes and other pathogens like HSV-1 and Chlamydia pneumonia has now become well established. In neurons infected by HSV-1 showed Aβ and hyperphosphorylated Tau accumulation. The expression of pro-inflammatory molecules have been found to be enhanced by specific bacterial ligands, and viral and bacterial DNA and RNA, thus activating the immune system. Aβ has now been established as anti-microbial peptide capable of inducing pore formation, thus justifying their infection-mediated accumulation. Thus, a proper combination of anti-inflammatory, anti-viral, and antibiotic therapeutics might potentially prevent the progression of AD. Here, we discussed the potential role of bacterial, fungi, and viral infections in AD causation and progression, and the potential-associated therapies to counter the AD condition.

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Abbreviations

ACh:

acetylcholine

ACV:

acyclovir

AD:

Alzheimer disease

Aβ:

amyloid-β

APOE-e4:

apolipoprotein E-e4

BBB:

blood brain barrier

CNS:

central nervous system

CMV:

cytomegalovirus

HSE:

herpes simplex encephalitis

HSV:

herpes simplex virus

HD:

Huntington’s disease

HHV:

human herpesvirus

IVIG:

intravenous immunoglobulin

IAV:

influenza A virus

MS:

multiple sclerosis

NDDs:

neurodegenerative disorders

NFTs:

neurofibrillary tangles

PAMP:

pathogen-associated molecular patterns

PD:

Parkinson’s disease

PBL:

peripheral blood leukocytes

ROS:

reactive oxygen species

VZV:

varicella zoster virus

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Acknowledgments

The authors are very grateful for the animal facilities that were provided by the center for preclinical trials of IPAC RAS.

Funding

This work was supported by the Russian Academic Excellence project “5-100” for the Sechenov University, Moscow, Russian Federation. This research was also supported in part by the RSF project #14-23-00160P and the scientific projects of IPAC (topics 48.8. and 48.9). Part of this work was also supported by the project of RAS Program Fundamental Research for Biomedical Technologies.

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Authors and Affiliations

  1. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

    Ghulam M. Ashraf

  2. I.M.Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str., 8, bld. 2, Moscow, Russia, 119991

    Vadim V. Tarasov, Vladimir N. Chubarev & Gjumrakch Aliev

  3. Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia, 142432

    Alfiya Makhmutovа, Sergey O. Bachurin & Gjumrakch Aliev

  4. Departamento de Ciencias Clínicas, Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia

    Marco Avila-Rodriguez

  5. GALLY International Biomedical Research Institute Inc., 7733 Louis Pasteur Drive, #330, San Antonio, TX, 78229, USA

    Gjumrakch Aliev

  6. School of Health Science and Healthcare Administration, University of Atlanta, E. Johns Crossing, #175, Johns Creek, GA, 30097, USA

    Gjumrakch Aliev

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  1. Ghulam M. Ashraf
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Correspondence to Gjumrakch Aliev.

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Ashraf, G.M., Tarasov, V.V., Makhmutovа, A. et al. The Possibility of an Infectious Etiology of Alzheimer Disease. Mol Neurobiol 56, 4479–4491 (2019). https://doi.org/10.1007/s12035-018-1388-y

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  • DOI: https://doi.org/10.1007/s12035-018-1388-y

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