Abstract
The disease known as late-onset Alzheimer’s disease is a neurodegenerative condition recognized as the single most commonform of senile dementia. The condition is sporadic and has been attributed to neuronal damage and loss, both of which have been linked to the accumulation of protein deposits in the brain. Significant progress has been made over the past two decades regarding our overall understanding of the apparently pathogenic entities that arise in the affected brain, both for early-onset disease, which constitutes approximately 5% of all cases, as well as late-onset disease, which constitutes the remainder of cases. Observable neuropathology includes: neurofibrillary tangles, neuropil threads, neuritic senile plaques and often deposits of amyloid around the cerebrovasculature. Although many studies have provided a relatively detailed knowledge of these putatively pathogenic entities, understanding of the events that initiate and support the biological processes generating them and the subsequent observable neuropathology and neurodegeneration remain limited. This is especially true in the case of late-onset disease. Although early-onset Alzheimer’s disease has been shown conclusively to have genetic roots, the detailed etiologic initiation of late-onset disease without such genetic origins has remained elusive. Over the last 15 years, current and ongoing work has implicated infection in the etiology and pathogenesis of late-onset dementia. Infectious agents reported to be associated with disease initiation are various, including several viruses and pathogenic bacterial species. We have reported extensively regarding an association between late-onset disease and infection with the intracellular bacterial pathogen Chlamydia pneumoniae. In this article, we review previously published data and recent results that support involvement of this unusual respiratory pathogen in disease induction and development. We further suggest several areas for future research that should elucidate details relating to those processes, and we argue for a change in the designation of the disease based on increased understanding of its clinical attributes.
Highlights
A longstanding idea in the medical literature is that a wide variety of chronic diseases could be caused or exacerbated by a microbial infection
On that basis we suggested the designation ‘‘late-onset dementia of the Alzheimer’s type’’ for the late-onset clinical entity, since it is more consistent with our current knowledge of the clinical and neuropathological underpinnings of the disease (Balin et al, 2017); in this article, we employ that designation, or late-onset dementia, throughout
In a separate study, it was shown that in patients with reactive arthritis who had DNA from C. pneumoniae in synovial tissues, 2/3 had one or more copies of the APOEε4 allele (Gérard et al, 1999). These and other observations discussed below clearly implicate a relationship between the APOEε4 allelic genotype and infection by C. pneumoniae; they suggest that both factors confer an increased risk for chronic disease genesis (Balin et al, 1998; Gérard et al, 1999)
Summary
A longstanding idea in the medical literature is that a wide variety of chronic diseases could be caused or exacerbated by a microbial infection. These and other observations discussed below clearly implicate a relationship between the APOEε4 allelic genotype and infection by C. pneumoniae; they suggest that both factors confer an increased risk for chronic disease genesis (Balin et al, 1998; Gérard et al, 1999) Not surprisingly, these initial studies and their implications suggesting that an infection with a common bacterium is involved in the origin of late-onset dementia instigated several other groups to attempt confirmation of the organism in brain tissues from other affected and control patient cases. Cell biological studies of both isolates demonstrated that they showed standard inclusion morphology and typical chlamydial morphology upon culture in human epithelial cells (HEp-2), astrocytes (U-87 MG) and microglial cells (CHME-5), as in a prior publication (Dreses-Werringloer et al, 2006)
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