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