# From routine periodontal therapy to Alzheimer's disease early detection: A scoping review

## TL;DR

This review explores how biomarkers from periodontal tissues and fluids could help detect Alzheimer's disease early, offering a new approach beyond traditional blood or saliva tests.

## Contribution

The paper introduces an AD-specificity pyramid framework to organize biomarker evidence from periodontal matrices for early Alzheimer's detection.

## Key findings

- Fourteen studies were identified, categorizing biomarkers into microbiome, molecular, and genetic/transcriptomic features.
- Biomarkers ranged from general inflammation markers to those closely linked to Alzheimer's core pathology.
- Cerebrospinal fluid amyloid-β positivity was the most brain-relevant anchor for validating periodontal biomarkers.

## Abstract

An epidemiological association has been observed between periodontitis and Alzheimer's disease (AD); however, salivary and blood assays often show low specificity. Periodontal tissues and fluids, which are routinely removed and discarded during periodontal treatment, may be collected to offer matrices useful for the early detection of AD. This study aimed to map current preclinical and clinical evidence on biomarkers measured in periodontal tissues and fluids for the early detection of AD and organize them within an AD-specificity pyramid anchored to brain-relevant endpoints. Following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses–Extension for Scoping Reviews) guidance, we searched PubMed, Scopus, and Web of Science (January 1, 2015–August 31, 2025) for preclinical and clinical studies measuring AD-relevant biomarkers in periodontal matrices. The protocol was pre-registered (OSF DOI: 10.17605/OSF.IO/EDVU9; August 20, 2025). Two reviewers extracted the data, and other two independently verified them. The findings were organized using a four-tier AD-specificity pyramid. Results: Fourteen studies met the inclusion criteria. The biomarkers from the included studies were clustered into microbiome features, molecular signals, and genetic/transcriptomic findings. Evidence ranged from Tier-1 contextual inflammation/pathogens to Tier-4 core-pathology adjacency; five studies incorporated clinical/biological anchoring, with cerebrospinal fluid amyloid-β positivity providing the most brain-relevant anchor. Periodontal matrices are practicable, high-signal sources for AD-relevant biomarkers. However, translational validation linking periodontal biomarkers to brain endpoints is needed to assess the feasibility of multi-tier and chairside panels for early AD detection as part of routine periodontal care.