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The Ocular Microbiome and Alzheimer’s Disease: Emerging Insights
Mishra SK, Ozkan J, Kim WS, Willcox M, Fu Y.. Preprints.org, 2026-07-22
Topic: Gut, metabolism and diet
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaques, neurofibrillary tau tangles, neuroinflammation, and progressive cognitive decline. Beyond these classical pathological features, emerging evidence implicates microbial dysbiosis as a contributing factor, with the gut and oral microbiomes currently providing the strongest evidence for microbiome AD associations. In contrast, the ocular microbiome represents a biologically plausible but largely unexplored candidate whose potential contribution to AD pathogenesis remains hypothetical and requires rigorous investigation. The ocular surface shares embryological, anatomical, and functional connections with the central nervous system, and the retina has emerged as a non-invasive window into neurodegenerative brain changes. Bacterial taxa detected in ocular specimens, including Cutibacterium acnes and Acinetobacter johnsonii, overlap with those reported in some studies of AD brain tissue, prompting speculation about an ocular–brain microbial interface. However, this overlap does not establish microbial trafficking, and no direct evidence currently supports the proposition that ocular microorganisms translocate to, colonize, or contribute causally to AD brain pathology. This review critically appraises the existing evidence, graded by methodological rigor and evidence strength, across gut, oral, nasal, ear, and ocular microbiome compartments. We address the substantial methodological challenges inherent in low-biomass microbiome research, emphasize the importance of distinguishing contamination artifacts from biological signals, and delineate the evidence gaps that separate association from causation. We conclude by proposing a research framework that places the ocular microbiome as an emerging hypothesis warranting experimental validation, rather than an established contributor to AD.
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APA 7th
Mishra, S. K., Ozkan, J., Kim, W. S., Willcox, M., & Fu, Y. (2026). The Ocular Microbiome and Alzheimer’s Disease: Emerging Insights. Preprints.org. https://doi.org/10.20944/preprints202607.1695.v1
Vancouver
Mishra SK, Ozkan J, Kim WS, Willcox M, Fu Y. The Ocular Microbiome and Alzheimer’s Disease: Emerging Insights. Preprints.org. 2026. doi:10.20944/preprints202607.1695.v1.
BibTeX
@article{mishra2026-59022093,
author = {Mishra, S. K. and Ozkan, J. and Kim, W. S. and Willcox, M. and Fu, Y.},
title = {{The Ocular Microbiome and Alzheimer’s Disease: Emerging Insights}},
journal = {Preprints.org},
year = {2026},
doi = {10.20944/preprints202607.1695.v1},
url = {https://doi.org/10.20944/preprints202607.1695.v1}
}
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Key findings
- We conclude by proposing a research framework that places the ocular microbiome as an emerging hypothesis warranting experimental validation, rather than an established contributor to AD.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Preprints.org) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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