Research Topic

An Infectious Origin of Alzheimer’s Disease: An End for This Devastating Disorder?

About this Research Topic

Dementia is declared by the WHO as a public health priority. The total number of patients with dementia worldwide is estimated at 35.6 million and is expected to nearly double every 20 years. The total estimated worldwide costs of dementia are around 604 billion per year. The challenges to governments to ...

Dementia is declared by the WHO as a public health priority. The total number of patients with dementia worldwide is estimated at 35.6 million and is expected to nearly double every 20 years. The total estimated worldwide costs of dementia are around 604 billion per year. The challenges to governments to respond to the growing number of patients with dementia are substantial. Alzheimer’s disease is the most frequent cause of dementia. If the cause of AD is not defined, and treatments to delay or prevent the disease are not provided, the world will face a health-care crisis by the middle of this century.

During infection, pathogens employ a broad range of strategies to overcome antigenic recognition, phagocytosis, and complement lysis. Blockade of the complement cascade allows their survival. In such conditions, even in immune competent hosts they spread freely and accumulate in the affected host tissues. Suppressing, subverting or evading host defenses they establish longstanding latent infections, inflammation, amyloid deposition and progressive tissue damage. Evidence of the involvement of microorganisms in chronic inflammatory disorders including AD is rapidly growing. It is well established that chronic bacterial infection can cause dementia and amyloid deposition in syphilitic dementia. In addition, Treponema pallidum reproduces all the defining hallmarks of AD, including beta amyloid deposition. A strong association between various spirochetal infections and AD fulfills Hill’s criteria for causality. Spirochetes evade host defenses, locate intracellularly, form more resistant atypical forms and notably biofilms, which help to sustain chronic infection and inflammation and explain the slowly progressive course of dementia in AD.

Spirochetes, Chlamydia pneumoniae, Porphyromonas gingivalis, Proprionobacterium acne, HSV-1 and various other viruses and pathogens might disseminate from the primary site of infection to the brain through systemic infection. As in syphilis, systemic infection and inflammation precede the development of dementia by years or decades. Detection of infection in its early, peripheral stage can hamper its dissemination to the CNS and prevent dementia. To consider co-infecting microorganisms is equally important, as multi-species biofilms may result in a higher resistance to treatments and a more severe dementia.

Amyloid proteins constitute a previously overlooked integral part of the cellular envelope of many bacteria. Amyloid fibril formation not only results in toxic aggregates, but provides biologically functional molecules, which contribute to bacterial virulence, to colonization of the host, invasion of host cells and biofilm formation.

Through pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) pathogens induce gene expression and activation of proinflammatory molecules by host cells. Both the classical and alternative complement pathways are activated in AD. Polymorphisms of inflammatory genes, PRRs, including TLRs, which recognize pathogen associated molecular patterns (PAMPs) are risk factors for infection and AD.

Infectious agents can initiate the degenerative process in AD, sustain chronic inflammation, and lead to progressive neuronal damage and amyloid deposition.

Most of the changes seen in AD, including up-regulated proinflammatory signaling, innate immune responses, increased oxidative stress, dementia, cortical atrophy, amyloidosis, and altered gene expression are all seen as consequence of a microbial infection. The outcome of infection is determined by the genetic predisposition of the patient, by the virulence and biology of the infecting agent, and by various environmental factors, such as exercise, stress and nutrition.

An infectious origin of AD opens solutions to prevent and eliminate dementia, as it happened in syphilitic dementia.


Keywords: Alzheimer's disease, Amyloid, Bacteria, Infection, Spirochetes, Dementia, Pathogens, Biofilm, Senile plaque, Beta amyloid, Tau, Inflammation, Bacterial amyloid, HSV1, Virus


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Recent Articles

Loading..

About Frontiers Research Topics

With their unique mixes of varied contributions from Original Research to Review Articles, Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author.

Topic Editors

Loading..

Submission Deadlines

31 January 2018 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

Loading..

Topic Editors

Loading..

Submission Deadlines

31 January 2018 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

Loading..
Loading..

total views article views article downloads topic views

}
 
Top countries
Top referring sites
Loading..

Comments

Loading..

Add a comment

Add comment
Back to top