Link Between Chronic Bacterial Inflammation and Alzheimer Disease

Abstract

Alzheimer's disease (AD) is a degenerative disease of brain that is associated with dementia, brain atrophy, accumulation of hyperphosphorylated tau protein and amyloid-beta peptide in hippocampus and cortex region of the brain. The development of AD is a multifactorial process that may also involve infection with bacterial pathogens. Recent studies suggest that bacteria including spirochetes have the potential to initiate cascade of events, leading to inflammatory condition of the central nervous system. Bacteria and spirochetes are activators of proinflammatory cytokines, generate free radicals, nitric oxide and further induction of apoptosis. Infection with these microbes may be considered as a risk factor for pathophysiology of AD or to cognitive changes. Recent studies have revealed that exposure to these microorganisms induces Aβ accumulation and tau protein phosphorylation, and chronic infections with these pathogenic bacteria can possibly contribute to progression of AD. In this article, we update and review the role of bacteria in the pathogenesis of AD resulting from initiation of cascade events in chronic inflammations and amyloidogenesis. Controlling these chronic infections with antibacterial or anti-inflammatory drugs will allow preventing inflammation, a risk factor for AD.

Gram-negative bacterial molecules associate with Alzheimer disease pathology

“…9–12 Infectious agents previously associated with AD include Spirochetes , P gingivalis , Borrelia burgdorferi , Chlamydophila pneumonia , Helicobacter pylori , C glabrata , various fungi, herpesviruses, and cytomegalovirus. 9–12 A major difference between previous studies and this one is that LPS colocalized with amyloid plaque and with perivascular amyloid in every AD brain.…”

“…8 Indeed, recent studies have demonstrated that sporadic late-onset AD is associated with infections. 9–12 However, a consistent link between these agents and AD neuropathology has not been demonstrated.…”

P. acnes-Driven Disease Pathology: Current Knowledge and Future Directions

“…What is generally not appreciated is that the brain is also susceptible to invading pathogens ranging from viruses and bacteria to fungi. These pathogens, or more specifically their endogenous components and/or metabolites, can produce central neurological deficits ranging from subtle signs of dementia and dystonia, which result from chronic, recurrent infection (De Chiara et al, 2012; Bibi et al, 2014), to more severe motor neuron disease as for example observed with the human endogenous retrovirus K (Li et al, 2015). Thus, it is clear that humans have a tremendously heavy systemic burden of microbes (Potgieter et al, 2015; Spadoni et al, 2015) which may incidentally contribute to the pathology of progressive neurodegenerative diseases with atypical protein component.…”

Necroptosis and Caspase-2-Mediated Apoptosis of Astrocytes and Neurons, but Not Microglia, of Rat Hippocampus and Parenchyma Caused by Angiostrongylus cantonensis Infection

“…The pathogenesis of diseases with enormous social importance, including cancer, HIV, autoimmune diseases and neurological disorders, is closely related to cell death (McConkey et al, 1996;Kaminskyy and Zhivotovsky, 2018). Accumulating studies have demonstrated that Alzheimer's (Bibi et al, 2014) and Parkinson's disease (Chen et al, 1995;Inoue, 2006) involve distinct types of cell death. Moreover, neurological dysfunction is thought to occur in CNS upon infection with bacteria (Baldi and Giambartolomei, 2013), viruses (An et al, 1996;Kaul and Lipton, 2006) or parasites (Eugenin et al, 2019) and might occur via apoptosis, necroptosis or autophagy (Tabor-Godwin et al, 2012).…”