Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 12;13(1):e12172.
doi: 10.1002/dad2.12172. eCollection 2021.

Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly

Angela R Kamer  1 , Smruti Pushalkar  2 , Deepthi Gulivindala  1 , Tracy Butler  3 , Yi Li  3 , Kumar Raghava Chowdary Annam  1 , Lidia Glodzik  3 , Karla V Ballman  4 , Patricia M Corby  5 , Kaj Blennow  6   7 , Henrik Zetterberg  6   7   8   9 , Deepak Saxena  2 , Mony J de Leon  3
Affiliations

Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly

Angela R Kamer et al. Alzheimers Dement (Amst). .

Abstract

Introduction: Periodontal disease is a chronic, inflammatory bacterial dysbiosis that is associated with both Alzheimer's disease (AD) and Down syndrome.

Methods: A total of 48 elderly cognitively normal subjects were evaluated for differences in subgingival periodontal bacteria (assayed by 16S rRNA sequencing) between cerebrospinal fluid (CSF) biomarker groups of amyloid and neurofibrillary pathology. A dysbiotic index (DI) was defined at the genus level as the abundance ratio of known periodontal bacteria to healthy bacteria. Analysis of variance/analysis of covariance (ANOVA/ANCOVA), linear discriminant effect-size analyses (LEfSe) were used to determine the bacterial genera and species differences between the CSF biomarker groups.

Results: At genera and species levels, higher subgingival periodontal dysbiosis was associated with reduced CSF amyloid beta (Aβ)42 (P = 0.02 and 0.01) but not with P-tau.

Discussion: We show a selective relationship between periodontal disease bacterial dysbiosis and CSF biomarkers of amyloidosis, but not for tau. Further modeling is needed to establish the direct link between oral bacteria and Aβ.

Keywords: 16S rRNA sequencing; Alzheimer's disease; CSF biomarkers; P‐tau; amyloid; infection; normal aging; oral bacterial dysbiosis; periodontitis.

PubMed Disclaimer

Conflict of interest statement

Kaj Blennow has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. Henrik Zetterberg has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). No conflict of interest is reported for any of the other authors.

Figures

FIGURE 1
FIGURE 1
Dysbiotic index in Amyloid (A) and P‐tau (B) groups. ANCOVA showed that Dysbiotic Index was statistically significant higher in Aβ+ group compared to the Aβ‐ group and this result maintained the significance after adjustment for APOE. However, Dysbiotic Index was not statistically significant between the P‐tau groups. Aβ‐ = amyloid‐: CSF Aβ42 ≥ 600 pg/mL; Aβ+ = Amyloid+: CSF Aβ42 < 600 pg/mL. ** = P < 0.01. P‐tau‐ = CSF P‐tau ≤ 45 pg/mL; P‐tau+ = CSF P‐tau > 45 pg/mL. Means and SE are presented
FIGURE 2
FIGURE 2
CSF Aβ42 in Dysbiotic groups. A: There was a statistically significant difference in the CSF Aβ42 between Low DI (n = 33) and High DI (n = 15) and B: Healthy cluster (HealthCL, n = 19) and periodontal‐associated cluster (PerioCL, n = 29) after adjustment for APOE (P = 0.037 and 0.035 respectively). Means and SE are presented. * = P < 0.05
FIGURE 3
FIGURE 3
Linear Discriminant Analysis (LDA) Effect Size (LEfSe) plot showing species relative abundance in amyloid‐ (AB_N) and amyloid+ (AB_P) groups. Lefse (P = 0.05 and LDA threshold = 2) shows that subgingival bacteria of amyloid+ subjects were enriched in species associated with periodontal disease while amyloid‐subjects were enriched in species associated with periodontal health (3A). Horizontal bars (red = AB_N; green = AB_P) represent the effect size for each specie. The LDA scores represent the log10 transformed LDA score. Negative as well as positive values denotes increased in abundance compared to the other group. Consistency in the relative abundance and pattern of the health associated bacterium Corynebacterium matruchotii and periodontal associated bacterium Fretibacterium fastidiosum are shown in Figure 3B and 3C. Each red bar of the histograms represents the relative abundance of one subject. The vertical thick black bar divides the amyloid‐ (AB_N) from amyloid+ (AB_P) subjects. The solid and dotted horizontal black lines indicate the mean and median relative abundance values for each group, respectively
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Jack CR Jr, Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207‐216. - PMC - PubMed
    1. Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015;14:388‐405. - PMC - PubMed
    1. Itzhaki RF, Lathe R, Balin BJ, et al. Microbes and Alzheimer's disease. J Alzheimers Dis. 2016;51:979‐984. - PMC - PubMed
    1. Bell JS, Spencer JI, Yates RL, Yee SA, Jacobs BM, DeLuca GC. Invited review: from nose to gut ‐ the role of the microbiome in neurological disease. Neuropathol Appl Neurobiol. 2019;. 45(3):195‐215. - PubMed
    1. Kamer AR, Craig RG, Niederman R, Fortea J, de Leon MJ. Periodontal disease as a possible cause for Alzheimer's disease. Periodontol 2000. 2020;83:242‐271. - PubMed

LinkOut - more resources