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Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease
Sparks Stein P, Steffen MJ, Smith C, Jicha G, Ebersole JL, Abner E, Dawson D.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2012-05-01
Topic: Amyloid, tau and blood-test diagnosis
Background Chronic inflammation in periodontal disease has been suggested as a potential risk factor in Alzheimer's disease (AD). The purpose of this study was to examine serum antibody levels to bacteria of periodontal disease in participants who eventually converted to AD compared with the antibody levels in control subjects. Methods Serum samples from 158 participants in the Biologically Resilient Adults in Neurological Studies research program at the University of Kentucky were analyzed for immunoglobulin G antibody levels to seven oral bacteria associated with periodontitis, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Treponema denticola, Fusobacterium nucleatum, Tannerella forsythia, and Prevotella intermedia. All 158 participants were cognitively intact at baseline venous blood draw. In all, 81 of the participants developed either mild cognitive impairment (MCI) or AD or both, and 77 controls remained cognitively intact in the years of follow-up. Antibody levels were compared between controls and subjects with AD at baseline draw and after conversion and controls and subjects with MCI at baseline draw and after conversion using the Wilcoxon rank-sum test. AD and MCI participants were not directly compared. Linear regression models were used to adjust for potential confounding. Results Antibody levels to F nucleatum and P intermedia were significantly increased (α = 0.05) at baseline serum draw in the patients with AD compared with controls. These results remained significant when controlling for baseline age, Mini-Mental State Examination score, and apolipoprotein epsilon 4 status. Conclusions This study provides initial data that demonstrate elevated antibodies to periodontal disease bacteria in subjects years before cognitive impairment and suggests that periodontal disease could potentially contribute to the risk of AD onset/progression. Additional cohort studies profiling oral clinical presentation with systemic response and AD and prospective studies to evaluate any cause-and-effect association are warranted.
Key findings
- The purpose of this study was to examine serum antibody levels to bacteria of periodontal disease in participants who eventually converted to AD compared with the antibody levels in control subjects.
- Methods Serum samples from 158 participants in the Biologically Resilient Adults in Neurological Studies research program at the University of Kentucky were analyzed for immunoglobulin G antibody levels to seven oral bacteria associated with periodontitis, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Treponema denticola, Fusobacterium nucleatum, Tannerella forsythia, and Prevotella intermedia.
- Results Antibody levels to F nucleatum and P intermedia were significantly increased (α = 0.05) at baseline serum draw in the patients with AD compared with controls.
- These results remained significant when controlling for baseline age, Mini-Mental State Examination score, and apolipoprotein epsilon 4 status.
- Conclusions This study provides initial data that demonstrate elevated antibodies to periodontal disease bacteria in subjects years before cognitive impairment and suggests that periodontal disease could potentially contribute to the risk of AD onset/progression.
Why it matters
In 158 people who were cognitively intact at the start, higher serum antibody levels to the periodontal bacterium Fusobacterium nucleatum were found in those who later developed Alzheimer's disease or mild cognitive impairment. This links a marker of periodontal infection to later cognitive decline, but it does not show that treating gum disease would prevent or cure Alzheimer's disease.
Study details
- Study designcohort study
- Participants158
- Evidence strengthModerate
How this study scored 63/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 158 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 465 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 29.1 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 5 / 6 | Cited 21.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 102 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Dolph R. Dawson: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Kentucky: institution h-index 824 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22546352) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Sparks Stein, P., Steffen, M. J., Smith, C., Jicha, G., Ebersole, J. L., Abner, E., et al. (2012). Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1016/j.jalz.2011.04.006
Vancouver
Sparks Stein P, Steffen MJ, Smith C, Jicha G, Ebersole JL, Abner E, et al. Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2012. doi:10.1016/j.jalz.2011.04.006. PMID: 22546352.
BibTeX
@article{sparksstein2012-22546352,
author = {Sparks Stein, P. and Steffen, M. J. and Smith, C. and Jicha, G. and Ebersole, J. L. and Abner, E. and Dawson, D.},
title = {{Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2012},
doi = {10.1016/j.jalz.2011.04.006},
pmid = {22546352},
url = {https://doi.org/10.1016/j.jalz.2011.04.006}
}
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