ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Different stages of Alzheimer's disease with periodontitis: clinical features and potential mechanisms involving gingipains, neuropathological biomarkers and neurological damage
Jing-hui Li 1
Teng-hong Lian 1,2
Peng Guo 1,2
Jing Li 1
Jing Qi 1
Ming-yue He 1
Dong-mei Luo 1
Ya-nan Zhang 3
Gai-fen Liu 1,4
Yue Huang 1,4,5
Wei-jia Zhang 1
Zi-jing Zheng 1
Hao Yue 1
Hui-ying Guan 1
Zhan Liu 1
Fan Zhang 1
Yao Meng 1
Wei Zhang 1
1. Department of Neurology, Beijing Tiantan Hospital Capital Medical University, Beijing, China
2. Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
3. Department of Blood Transfusion, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
4. China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
5. Department of Pharmacology, School of Medical Sciences, Faculty of Medicine & Health, UNSW Sydney, China
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Abstract
Background: Alzheimer's disease (AD) and periodontitis are common in older adults aged over 65 years. However, the clinical features and mechanisms at mild cognitive impairment and dementia due to AD (AD-MCI and AD-D) stages remain unknown. Methods: In 110 patients with AD-MCI and AD-D, oral hygiene, periodontitis status, clinical symptoms and the levels of gingipain, neuropathological biomarkers and neurological damage indicators in cerebrospinal fluid were evaluated. Results: The frequency of periodontitis was 38.18% in the AD-MCI group and 67.27% in the AD-D group. The AD-MCI with periodontitis group had significantly worse cognition and lower β- amyloid(Aβ) level than those without periodontitis (all P<0.05). The AD-D with periodontitis group had further impaired cognition and more severe neuropsychiatric symptoms. significant correlation of gingipain K (K-GP) with Aβ level, phosphorylated tau 199 and synaptosomal-associated protein 25 levels in cerebrospinal fluid (all P<0.05). Conclusions: K-GP plays a significant role in AD with periodontitis, and is associated with AD pathology and impairs cognition at the MCI stage. Periodontitis is more prevalent and severe in AD patients. K-GP contributes to the exacerbation of AD pathology and neurodegeneration, and is potentially involved in the aggravation of symptoms at the dementia stage.
Summary
Keywords
Alzheimer's disease, clinicalfeatures and potential mechanisms, Dementia, Mild Cognitive Impairment, Periodontitis
Received
01 November 2025
Accepted
20 February 2026
Copyright
© 2026 Li, Lian, Guo, Li, Qi, He, Luo, Zhang, Liu, Huang, Zhang, Zheng, Yue, Guan, Liu, Zhang, Meng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Wei Zhang
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