A Cedars-Sinai study published in Nature Communications in January 2026 has indicated that chlamydia pneumoniae, the common bacterium which can cause respiratory infections such as bronchitis and pneumonia, could also potentially be used as a retinal biomarker for Alzheimer’s disease and other neurodegenerative diseases.
To learn more, we spoke with authors Maya Koronyo-Hamaoui and Timothy R. Crother about their study findings.
What advantages does the retina offer for studying inflammatory and degenerative processes linked to neurodegenerative diseases like Alzheimer’s?
The retina is a central nervous system tissue with shared embryologic origin, neurovascular organization, and innate immune biology that parallels key processes in the brain in Alzheimer’s disease. Critically, it is uniquely accessible: it can be examined noninvasively, repeatedly, and at high spatial resolution using established clinical imaging modalities (e.g., optical confocal imaging, OCT, and OCT-angiography). This enables longitudinal monitoring of neurodegenerative- and inflammation-associated changes over time, including neuronal integrity, vascular alterations, and inflammatory signatures, in a way that is not currently feasible for most brain regions in routine clinical practice.
In addition, the retina’s well-layered architecture and defined cell populations provide an excellent substrate to map pathology to specific cell types and compartments, which can help dissect mechanisms linking inflammation to neurodegeneration.
Chlamydia pneumoniae has already been well characterized in AD brains. What made you suspect it might play an active role rather than being a bystander in disease processes?
We were motivated by several converging observations that argue for a mechanistic role rather than passive “bystander” presence. First, Chlamydia pneumoniae is a chronic, obligate intracellular pathogen that can persist in host cells and is a potent trigger of innate immune signaling. Beyond Alzheimer’s, it has been linked to chronic inflammatory conditions such as asthma and atherosclerosis, where experimental models support an exacerbating, disease-amplifying effect of infection. Second, Alzheimer’s disease is increasingly understood as a condition in which sustained innate immune activation and neuroinflammation meaningfully contribute to neurodegeneration – and importantly, we, and others, have shown related inflammatory signatures in the Alzheimer’s retina. That makes a persistent infectious stimulus biologically plausible as an upstream driver of the inflammatory cascades implicated in disease progression. Third, our human tissue data were not consistent with an incidental finding: pathogen burden tracked with clinical and pathological severity, including more advanced brain pathology and worse cognitive indices, and it aligned with robust inflammasome-associated activation (including signatures consistent with NLRP3 pathway engagement and downstream inflammatory effector responses).
Finally, we strengthened the clinical observations with experimental evidence: in complementary models, infection was sufficient to trigger inflammatory activation and worsen Alzheimer’s-relevant pathology and functional outcomes. Together, these findings support the view that Chlamydia pneumoniae can act as a disease-modifying amplifier in at least a subset of patients, rather than being merely an inert bystander.
Which retinal cell types appeared most affected by Chlamydia pneumoniae, and how might this influence retinal integrity or function?
In our analyses, the infection signal and associated inflammatory activation localized to retinal compartments and cell populations relevant to innate immune responses and neurovascular/neuronal health. The most consistent pattern was involvement of cells that participate in host defense and inflammatory signaling (including myeloid-lineage immune cells and glia), alongside effects in neuronal layers that are vulnerable in Alzheimer’s-related retinal pathology (RGCs, INL cells).
Mechanistically, persistent intracellular infection in these compartments can promote local IL-1 family inflammatory signaling, inflammasome activation, and cell stress/death pathways. Over time, this type of chronic inflammatory milieu can plausibly impair synaptic and neuronal integrity, disrupt neurovascular unit function, and contribute to structural and functional changes detectable by retinal imaging, and potentially linked to visual and cognitive phenotypes.
In the future, do you think retinal biomarkers could complement neurologic assessment in patients at risk for cognitive decline?
Yes. We view retinal biomarkers as complementary rather than replacing established neurologic evaluation. The retina may offer scalable, repeatable measures that could: 1) enrich risk stratification (e.g., who warrants closer cognitive follow-up); 2) provide longitudinal “trajectory” information (i.e., change over time); and 3) potentially reflect mechanistically relevant pathways, such as neuroinflammation, vascular dysfunction, and proteinopathy-associated neurodegeneration.
Importantly, this will require rigorous standardization, validation across diverse cohorts, and careful integration with clinical, neuropsychological, and established fluid/imaging biomarkers.
Are there specific retinal changes ophthalmologists should be looking out for that could warrant broader neurologic assessment?
Our study supports the broader concept that Alzheimer’s-related biology can be reflected in the retina, including inflammatory activation and neurodegeneration-relevant changes. In practice today, ophthalmologists should be cautious about over-interpreting any single retinal feature as “Alzheimer’s-specific.”
That said, in older adults – especially those with additional risk factors – combinations of findings such as unexplained inner retinal neurodegenerative changes (e.g., thinning or structural abnormalities consistent with ganglion cell/inner retinal vulnerability), microvascular alterations on OCT-A, unexplained signs of “aggregated proteins/spots,” and evidence consistent with heightened inflammatory stress could reasonably prompt consideration of a broader systemic/neurologic context. The key is not a single sign, but patterns, progression, and clinical context, ideally in collaboration with neurology and primary care.
What further steps are needed before ophthalmologists can integrate retinal biomarkers into routine clinical practice for neurodegenerative risk assessment?
Several steps are essential:
1. Prospective, longitudinal studies that link retinal measures to cognitive trajectories and validated Alzheimer’s biomarkers (fluid biomarkers, PET, MRI) across disease stages.
2. Standardized acquisition and analysis pipelines (device harmonization, segmentation/QC standards, normative reference ranges).
3. Demonstration of clinical utility: defining what retinal findings add beyond age, comorbidities, and existing neurologic tools; and showing they change management in a beneficial way.
4. Clear guidelines to address specificity and confounding (ocular disease, vascular risk factors, glaucoma, diabetes), and to establish referral pathways that are clinically appropriate and ethically responsible.
5. Replication across multi-center, diverse populations, with attention to generalizability and health equity.
How do you hope this research might influence future collaboration between ophthalmology and neurology?
We hope it encourages a more integrated “eye–brain health” model. Ophthalmology is increasingly data-rich (high-resolution structural and vascular imaging), and neurology is rapidly advancing in biomarker-driven risk assessment. Collaboration could enable bidirectional benefits: ophthalmology may help identify high-risk patterns earlier and monitor change more frequently, while neurology can provide diagnostic context, cognitive assessment, and access to systemic biomarker frameworks. Practically, this could lead to shared screening/referral algorithms for ageing patients, joint clinical research cohorts, and integrated trials where retinal readouts help track therapeutic engagement of inflammatory or neurodegenerative pathways.
What would be the single most important takeaway from your study?
The retina can reflect biologically meaningful Alzheimer’s-related inflammatory pathways, including pathogen-associated innate immune activation, and therefore offers a powerful, accessible window into mechanisms that may contribute to neurodegeneration in a subset of patients.
For ophthalmologists, the key message is that the eye may provide actionable information for cross-disciplinary risk assessment and longitudinal monitoring, once validated and standardized, supporting closer collaboration with neurology in aging care.
Is there anything else you would like to add?
Two important points. First, our findings do not imply that all Alzheimer’s disease is driven by infection; rather, they support the concept of biological heterogeneity and suggest that infection-triggered inflammasome activation may represent one contributory pathway in a subset of patients. Second, translation should be careful and evidence-based: retinal biomarkers are promising, but specificity, confounders, and clinical utility must be established before routine adoption.
We are enthusiastic about the potential for multi-modal approaches, integrating retinal imaging with systemic biomarkers and clinical phenotyping, to improve early detection, stratification, and eventually precision prevention/intervention strategies.
