Background/Aim: Chlamydia pneumoniae (C. pneumoniae) is implicated in the pathogenesis of Alzheimer’s disease (AD). Chlamydial elementary and reticulate bodies have been identified in tissues from afflicted AD brain regions by electron and immunoelectron microscopy, whereas similar tests of non-AD brains were negative for the bacterium. Studies in mice have shown that C. pneumoniae can rapidly penetrate the central nervous system by entering glia and causing beta amyloid deposition via the nerves between the nasal cavity and the brain, which serve as invasion pathways.
Materials and Methods: We used data from the UK Biobank (UKBB) to assess the relationship of chlamydia and AD. Circulating C. pneumoniae antigen measurements were not available, but UKBB data field 23037 held measurements of PorB antigen for Chlamydia trachomatis (C. trachomatis). We used C. trachomatis as a surrogate for C. pneumoniae since serum cross-reactivity to C. trachomatis and C. pneumoniae antigens occurs in patients with documented infection and in healthy children as revealed by microimmunofluorescence and immunoblotting techniques. Single nucleotide polymorphism (SNP) data for rs429358 and rs7412 were used to impute ApoE genotypes.
Results: PorB antigen levels for C. trachomatis were significantly higher in subjects with AD (p=0.007). PorB antigen levels were not related to ApoE genotype (e3e3, e3e4, e4e4) p=0.783. To control for the effects of age, sex, educational level, and apoE genotype, logistic regression analysis was performed. AD was the dependent variable. Independent variables were sqrt PorB antigen for C. trachomatis, age, sex, educational level, apoE genotype. AD odds ratio (OR) increased 1.156 for each unit increase of sqrt PorB antigen for C. trachomatis and the effect was significant (p=0.004).
Conclusion: PorB antigens for C. trachomatis being significantly higher in subjects with AD, corroborates previous studies demonstrating that C. pneumoniae inflammation appears to play a role in AD development. AD may result from the reactivation of embryologic processes and pathways silenced at birth. A trigger for the reactivation may be bacterial or viral infections. Further studies are warranted.
Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk
Scientific Reports volume 12, Article number: 2759 (2022)
Chlamydia pneumoniae is a respiratory tract pathogen but can also infect the central nervous system (CNS). Recently, the link between C. pneumoniae CNS infection and late-onset dementia has become increasingly evident. In mice, CNS infection has been shown to occur weeks to months after intranasal inoculation. By isolating live C. pneumoniae from tissues and using immunohistochemistry, we show that C. pneumoniae can infect the olfactory and trigeminal nerves, olfactory bulb and brain within 72 h in mice. C. pneumoniae infection also resulted in dysregulation of key pathways involved in Alzheimer’s disease pathogenesis at 7 and 28 days after inoculation. Interestingly, amyloid beta accumulations were also detected adjacent to the C. pneumoniae inclusions in the olfactory system. Furthermore, injury to the nasal epithelium resulted in increased peripheral nerve and olfactory bulb infection, but did not alter general CNS infection. In vitro, C. pneumoniae was able to infect peripheral nerve and CNS glia.
In summary, the nerves extending between the nasal cavity and the brain constitute invasion paths by which C. pneumoniae can rapidly invade the CNS likely by surviving in glia and leading to Aβ deposition.
- https://pubmed.ncbi.nlm.nih.gov/23400696/ Excerpt:
- Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae…..Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult.
- Two other studies have come to the same conclusion: that there exists a high prevalence and diversity of Chlamydiales DNA in ticks and the very real possibility of human infection. https://www.ncbi.nlm.nih.gov/pubmed/24698831 and https://www.ncbi.nlm.nih.gov/pubmed/26386066