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Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model.

Overview

Authors: Momoko Nakahara1, Kota Kataoka2, Takayuki Maruyama1, Mohammad Nurhamim3, Yixuan Zhang3, Daiki Fukuhara4, Yoko Uchida-Fukuhara5, Md Monirul Islam6, Manabu Morita7, Takashi Saito8, Daisuke Ekuni1
  1. Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (T.M.); (D.E.)
  2. Department of Preventive Dentistry, Division of Dentistry, Medical Development Field, Okayama University, Okayama 700-8558, Japan
  3. Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan; (M.N.); (Y.Z.)
  4. Department of Preventive Dentistry, Dental School, Okayama University, Okayama 700-8558, Japan
  5. Laboratory of Biological Anthropology, Research Center for Integrative Evolutionary Science, The Graduate University for Advanced Studies, SOKENDAI, Hayama 240-0193, Japan
  6. Centre for Policy Studies, University College Cork, T12 K8AF Cork, Ireland
  7. Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care, Takarazuka 531-0071, Japan
  8. Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Journal: International journal of molecular sciences, volume 27, issue 17, article 7542
Dates: received 3 July 2026; accepted 21 August 2026; published online 23 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.3390/ijms27177542 · PMID 42737444 · PMCID PMC13565786 · OpenAlex W7204112316
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), other condition (population), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Preprocessing
Keywords: Alzheimer’s disease, periodontitis, diabetes mellitus, microRNA, mRNA
MeSH: Alzheimer Disease*, Diabetes Mellitus*, Periodontitis*, Animals, Basic Helix-Loop-Helix Proteins, Disease Models, Animal, Hippocampus, Male, Mice, MicroRNAs, RNA, Messenger (* major topic)
Topic: Oral microbiology and periodontitis research (Periodontics, Dentistry), according to OpenAlex
Funding: Japan Society for the Promotion of Science (JP18H03014,JP24K13278,JP26K02602)
Citations: not cited yet (Europe PMC); 166 references in the paper

Abstract

The purpose of the present study was to investigate how periodontitis and diabetes mellitus (DM) are associated with Alzheimer’s disease (AD) through microRNA (miRNA) using AD model mice. The experimental period was 8 weeks. Twenty-four male knock-in mice (B6-AppNL-G-F/NL-G-F/J) were divided into four groups: control group fed a normal diet (C), DM group fed a high-fat/sucrose diet (DM), periodontitis (P) group, and DM + periodontitis (DM+P) group. Memory performance was compared using the Y-maze test. Next-generation sequencing was performed on brain samples, and fold changes in miRNA expression were calculated by comparing the DM+P and C groups. Integrated miRNA–mRNA analysis identified putative miRNA-targeted mRNAs, and protein expression of the top candidate gene was assessed. Memory function in the DM+P group was significantly lower than in the C group. Among the seven mRNAs identified by the integrated analysis, Neurod1 showed the greatest decrease in expression, and it was predicted to be regulated by miR-693-3p. Neurod1 protein expression in the hippocampus was significantly lower in the DM+P group than the C group. Our results suggest that the combined exposure to periodontitis and DM was associated with AD-like pathological changes and identified the miR-693-3p/Neurod1 pair as a candidate regulatory axis.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data Availability Statement

The raw sequencing data generated in this study have been deposited in the NCBI Gene Expression Omnibus (GEO) under accession numbers GSE344050 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE344050) for RNA-seq and GSE344051 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE344051) for miRNA-seq.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 5 keywords, 11 MeSH terms, 1 funder, 166 references.

Cite

This paper

Nakahara, M., Kataoka, K., Maruyama, T., Nurhamim, M., Zhang, Y., Fukuhara, D., Uchida-Fukuhara, Y., Islam, M. M., Morita, M., Saito, T., & Ekuni, D. (2026). Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model. International journal of molecular sciences, 27(17), 7542. https://doi.org/10.3390/ijms27177542

BibTeX

@article{nakahara2026assessment,
author = {Nakahara, Momoko and Kataoka, Kota and Maruyama, Takayuki and Nurhamim, Mohammad and Zhang, Yixuan and Fukuhara, Daiki and Uchida-Fukuhara, Yoko and Islam, Md Monirul and Morita, Manabu and Saito, Takashi and Ekuni, Daisuke},
title = {{Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model}},
journal = {International journal of molecular sciences},
year = {2026},
month = aug,
volume = {27},
number = {17},
pages = {7542},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
issn = {1422-0067},
doi = {10.3390/ijms27177542},
url = {https://doi.org/10.3390/ijms27177542},
pmid = {42737444},
pmcid = {PMC13565786}
}

RIS

TY - JOUR
AU - Nakahara, Momoko
AU - Kataoka, Kota
AU - Maruyama, Takayuki
AU - Nurhamim, Mohammad
AU - Zhang, Yixuan
AU - Fukuhara, Daiki
AU - Uchida-Fukuhara, Yoko
AU - Islam, Md Monirul
AU - Morita, Manabu
AU - Saito, Takashi
AU - Ekuni, Daisuke
TI - Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model
T2 - International journal of molecular sciences
J2 - Int J Mol Sci
PY - 2026
DA - 2026/08/23
VL - 27
IS - 17
SP - 7542
SN - 1422-0067
PB - Multidisciplinary Digital Publishing Institute (MDPI)
DO - 10.3390/ijms27177542
UR - https://doi.org/10.3390/ijms27177542
LA - en
ER -

CSL-JSON

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