The possibility of an infectious etiology of several chronic diseases, including AD, has long been debated. Alzheimer, himself, over 100 years ago studied Treponema pallidum, the causative agent of syphilis, a spirochete later associated with dementia. Oskar Fischer, a contemporary of Alois Alzheimer and also a psychiatrist and neuropathologist, also suggested that microorganisms could form plaques in brain tissues. Sporadic late-onset Alzheimer’s disease, accounting for ~95% -98% of all cases of Alzheimer’s disease, is thought to arise due to a multi-factorial interplay between genetic and environmental factors. Speculation as to which environmental factors have a great impact on the pathogenesis of this disease has resulted in studies of infectious disease. This is a rational approach as different types of infections have been associated with dementing illnesses, including infection with Treponema pallidum, mentioned previously, as well as Cryptococcus neoformans, measles virus, and HIV. Early studies of infection directly related to Alzheimer’s disease attempted to correlate viral infection with late-onset disease. Of the viruses considered were: cytomegalovirus, measles virus, poliovirus, adenoviruses, hepatitis B virus, and the influenza A and B viruses. There was no association with disease determined for these viruses. Later and more recent studies have found evidence for direct brain infection in AD with HSV1, Borrelia burgdorferi, and Chlamydia pneumoniae. There are some reports that even systemic infections may correlate to increased incidence of AD and infection with Helicobacter pylori, the agent of gastric ulcers and Porphyromonas gingivalis, an agent of periodontitis, have been studied in late-onset disease. Furthermore, studies on the gut microbiota and their role in AD pathogenesis is now being explored. Given these reports and the need to identify and understand causative factors for sporadic late-onset AD, much inquiry is needed to determine the mechanisms by which these different infections can initiate and/or participate in the pathogenesis of AD.
Interestingly, when one considers factors that may drive the accumulation of amyloid and tau in AD, infectious triggers are some of the most significant and logical choices. In particular, the organisms likely to be involved in AD are those that can evade host immune defenses, gain entry to specific selectively vulnerable regions of the brain, and establish chronic/persistent and/or latent infection. Upon considering the other risk factors found in AD, infection may be the central hub connecting these factors. Currently, evidence from research on numerous infectious agents, links a number of other risk factors with infection to the pathogenesis of AD. Linkage has been identified to risk factors including ApoE4 expression, chronic neuroinflammation, autoimmune mechanisms, oxidative and mitochondrial damage, cardiovascular factors, diabetes with insulin resistance, trauma to the blood brain barrier and selectively vulnerable brain insult. Thus, infection actually may be the overarching “unifying hypothesis” for sporadic late-onset AD, rather than other more mainstream hypotheses. The current Research Topic in Frontiers in Aging Neuroscience will address the many proposed infectious processes leading or contributing to the pathogenesis of Alzheimer’s disease.
The possibility of an infectious etiology of several chronic diseases, including AD, has long been debated. Alzheimer, himself, over 100 years ago studied Treponema pallidum, the causative agent of syphilis, a spirochete later associated with dementia. Oskar Fischer, a contemporary of Alois Alzheimer and also a psychiatrist and neuropathologist, also suggested that microorganisms could form plaques in brain tissues. Sporadic late-onset Alzheimer’s disease, accounting for ~95% -98% of all cases of Alzheimer’s disease, is thought to arise due to a multi-factorial interplay between genetic and environmental factors. Speculation as to which environmental factors have a great impact on the pathogenesis of this disease has resulted in studies of infectious disease. This is a rational approach as different types of infections have been associated with dementing illnesses, including infection with Treponema pallidum, mentioned previously, as well as Cryptococcus neoformans, measles virus, and HIV. Early studies of infection directly related to Alzheimer’s disease attempted to correlate viral infection with late-onset disease. Of the viruses considered were: cytomegalovirus, measles virus, poliovirus, adenoviruses, hepatitis B virus, and the influenza A and B viruses. There was no association with disease determined for these viruses. Later and more recent studies have found evidence for direct brain infection in AD with HSV1, Borrelia burgdorferi, and Chlamydia pneumoniae. There are some reports that even systemic infections may correlate to increased incidence of AD and infection with Helicobacter pylori, the agent of gastric ulcers and Porphyromonas gingivalis, an agent of periodontitis, have been studied in late-onset disease. Furthermore, studies on the gut microbiota and their role in AD pathogenesis is now being explored. Given these reports and the need to identify and understand causative factors for sporadic late-onset AD, much inquiry is needed to determine the mechanisms by which these different infections can initiate and/or participate in the pathogenesis of AD.
Interestingly, when one considers factors that may drive the accumulation of amyloid and tau in AD, infectious triggers are some of the most significant and logical choices. In particular, the organisms likely to be involved in AD are those that can evade host immune defenses, gain entry to specific selectively vulnerable regions of the brain, and establish chronic/persistent and/or latent infection. Upon considering the other risk factors found in AD, infection may be the central hub connecting these factors. Currently, evidence from research on numerous infectious agents, links a number of other risk factors with infection to the pathogenesis of AD. Linkage has been identified to risk factors including ApoE4 expression, chronic neuroinflammation, autoimmune mechanisms, oxidative and mitochondrial damage, cardiovascular factors, diabetes with insulin resistance, trauma to the blood brain barrier and selectively vulnerable brain insult. Thus, infection actually may be the overarching “unifying hypothesis” for sporadic late-onset AD, rather than other more mainstream hypotheses. The current Research Topic in Frontiers in Aging Neuroscience will address the many proposed infectious processes leading or contributing to the pathogenesis of Alzheimer’s disease.