Periodontal dysbiosis associates with reduced csf aβ42 in cognitively normal elderly

Angela R. Kamer; Smruti Pushalkar; Deepthi Gulivindala; Tracy Butler; Yi Li; Kumar Raghava Chowdary Annam; Lidia Glodzik; Karla V. Ballman; Patricia M. Corby; Kaj Blennow; Henrik Zetterberg; Deepak Saxena; Mony J. de Leon

doi:10.1002/dad2.12172

Periodontal dysbiosis associates with reduced csf aβ42 in cognitively normal elderly

Angela R. Kamer, Smruti Pushalkar, Deepthi Gulivindala, Tracy Butler, Yi Li, Kumar Raghava Chowdary Annam, Lidia Glodzik, Karla V. Ballman, Patricia M. Corby, Kaj Blennow, Henrik Zetterberg, Deepak Saxena, Mony J. de Leon

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	e12172
Journal	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume	13
Issue number	1
DOIs	https://doi.org/10.1002/dad2.12172
State	Published - 2021

Keywords

16S rRNA sequencing
Alzheimer’s disease
Amyloid
CSF biomarkers
Infection
Normal aging
Oral bacterial dysbiosis
P-tau
Periodontitis

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

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10.1002/dad2.12172

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Kamer, A. R., Pushalkar, S., Gulivindala, D., Butler, T., Li, Y., Annam, K. R. C., Glodzik, L., Ballman, K. V., Corby, P. M., Blennow, K., Zetterberg, H., Saxena, D., & de Leon, M. J. (2021). Periodontal dysbiosis associates with reduced csf aβ42 in cognitively normal elderly. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 13(1), Article e12172. https://doi.org/10.1002/dad2.12172

Kamer, AR, Pushalkar, S, Gulivindala, D, Butler, T, Li, Y, Annam, KRC, Glodzik, L, Ballman, KV, Corby, PM, Blennow, K, Zetterberg, H, Saxena, D & de Leon, MJ 2021, 'Periodontal dysbiosis associates with reduced csf aβ42 in cognitively normal elderly', Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, vol. 13, no. 1, e12172. https://doi.org/10.1002/dad2.12172

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abstract = "Introduction: Periodontal disease is a chronic, inflammatory bacterial dysbiosis that is associated with both Alzheimer{\textquoteright}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{\textquoteright}s disease, Amyloid, CSF biomarkers, Infection, Normal aging, Oral bacterial dysbiosis, P-tau, Periodontitis",

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AU - Li, Yi

AU - Annam, Kumar Raghava Chowdary

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AU - Ballman, Karla V.

AU - Corby, Patricia M.

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Saxena, Deepak

AU - de Leon, Mony J.

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AB - 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.

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Periodontal dysbiosis associates with reduced csf aβ42 in cognitively normal elderly

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