Alzheimer’s biomarkers in dental practice: Is innovation outpacing readiness?

To the editor, 

Let me begin by saying my passion has been advancing Alzheimer’s prevention through the lens of oral health, a focus I have pursued for nearly a decade. During that time, I have worked across both the dental profession and the preventive neurology space to help bridge disciplines, translate emerging science, and promote earlier risk recognition. 

As enthusiasm grows for precision medicine and Alzheimer’s prevention, some in my own dental field have proposed expanding biomarker testing—including APOE genotyping and blood-based phosphorylated Tau assays—into dental practices. While interdisciplinary innovation should be welcomed, the scientific and ethical complexities of these tests warrant far greater caution than is sometimes acknowledged. 

The role of dentistry in systemic health screening 

Dental professionals routinely identify hypertension, diabetes risk, sleep-disordered breathing indicators, inflammatory burden, medication effects, and barriers to care. Yet a practical reality remains: many practices still do not consistently perform blood pressure measurements, airway assessments, or utilize available salivary diagnostics that can aid periodontal diagnosis, microbial risk stratification, and treatment planning.  

Before embracing complex neurodegenerative biomarker programs, our profession should ask whether we are fully leveraging the simpler, evidence-based tools already within reach. Inflammatory host-response markers, periodontal pathogen burden, airway risk indicators, salivary molecular diagnostics, and vascular screening may offer more immediate and clinically relevant value to everyday dental practice than speculative expansion into neurodegenerative screening.^1,2 

Examining Tau testing 

APOE status is not a diagnosis; it is a probabilistic genetic risk marker associated with altered Alzheimer’s disease risk, not certainty of disease. Risk is further influenced by the interaction of other genetic variants affecting inflammation, lipid transport, mitochondrial function, immune response, vascular biology, and amyloid processing.

Markers like TREM2, APOC1, TOMM40, Klotho (KL), CLU, BIN1, ABCA7, CR1, PICALM, and SORL1 may further modify susceptibility, resilience, age of onset, or disease trajectory. Results may affect not only the patient, but also family members, future planning, emotional well-being, and perceptions of cognitive destiny. Such testing requires informed consent that addresses uncertainty, limitations, privacy concerns, and psychosocial impact.^3-8 

Blood-based phosphorylated Tau testing is equally nuanced. The phrase “blood Tau test” is often used as though it refers to a single standardized tool. It does not. Multiple analytes exist, including p-Tau181, p-Tau217, and p-Tau231, each with differing performance characteristics, proposed clinical roles, and evidence bases. Some appear more useful in identifying Alzheimer’s-type pathology, others may rise earlier in disease trajectories, and none should be interpreted in isolation.^9-12 

2023 reviews have highlighted the rapid progress of blood-based Alzheimer’s biomarkers, particularly plasma p-Tau217 and related assays. At the same time, these publications emphasize the need for harmonization, validated cut points, pre-analytical consistency, and careful clinical interpretation before widespread deployment. Those caveats deserve serious attention when considering use in routine dental practice.^13,14 

Specimen type also matters. Whole blood, plasma, and serum are not interchangeable matrices. Many leading studies and evolving clinical models rely on plasma rather than serum because clotting processes, cellular release of proteins, and handling variables can alter measured concentrations. Plasma-based p-Tau assays currently have stronger validation in much of the published literature, while serum performance can be more variable and assay-dependent.^9-14 A result from one matrix cannot automatically be compared with another. 

Assay platform matters as well. Different laboratories may use ultra-sensitive immunoassays, proprietary algorithms, or mass spectrometry-based methods. These approaches differ in calibration standards, antibodies, detection thresholds, units of measure, and reference intervals. A numeric result from one laboratory may not translate directly to another. Without assay-specific validation, clinicians risk overconfidence in numbers that are not universally comparable.^10-14

Pre-analytical variables are another major concern and are frequently underappreciated outside specialty settings. Time from draw to centrifugation, tube type, storage temperature, freeze-thaw cycles, hemolysis, transport conditions, and processing delays can all influence biomarker integrity. These are not technical footnotes; they are central determinants of result reliability.¹⁴ 

Clinical context is equally critical. Elevated p-Tau values should not be equated with dementia, nor should “normal” values be viewed as blanket reassurance. For example, pTau217 can indicate amyloid pathology in the brain but has no further explanation or description of any further pathology or disease indication. Chronic kidney disease (CKD) can increase multiple biomarkers of neurodegenerative disease, but those are false positives in many cases.

Cerebral amyloid angiopathy (CAA) can show high pTau217, but the amyloid ratio remains in a healthy range. Interpretation must consider symptoms, functional status, cognitive testing, age, vascular disease, kidney disease, traumatic brain injury history, other neurodegenerative disorders, medications, and the need for confirmatory imaging or specialist evaluation.^9-13 

The central question is not whether a dental office can send someone for a laboratory-based blood test. It is whether a typical dental setting is structured to provide pre-test counseling, manage uncertainty, interpret assay limitations, protect sensitive data, and coordinate appropriate neurologic follow-up. In many cases, the answer is no. 

False positives may generate unnecessary fear, cascades of testing, and specialty referrals. False negatives may create misplaced reassurance and delay evaluation. Commercialization of complex biomarker panels as premium wellness offerings raises additional concerns regarding patient vulnerability and informed decision-making.

How dentistry can contribute meaningfully to brain-health prevention 

Dentistry can make a difference in brain-health prevention through evidence-based pathways already within scope: periodontal inflammation reduction, blood pressure screening, sleep apnea recognition, smoking cessation, nutrition counseling, xerostomia management, and collaboration with primary care and neurology partners. This includes a clearer recognition of the clinically relevant relationships between periodontal disease and cardiovascular health, including associations with atherosclerosis, stroke risk, atrial fibrillation, and broader vascular dysfunction.^1,2 

If advanced biomarker programs are considered, they should occur only within rigorous interdisciplinary frameworks using validated laboratories, explicit informed consent, qualified medical interpretation, privacy safeguards, and defined referral pathways. Without those protections, we risk outrunning both the evidence and the infrastructure required to use it responsibly. 

Personally, I hope our profession keeps a stronger focus on the fundamentals that can change lives now: blood pressure assessment, chairside glucose awareness, oral pathogen testing, and host-response measures like neutrophil activity. Advancing these practical, evidence-based tools could elevate dentistry in immeasurable ways. 

Innovation is important. Precision is essential. Prudence remains indispensable. 

Sincerely, 

Anne O. Rice, RDH, BS, FAAOSH, CDP 

References:

1. Giannobile WV. Salivary diagnostics for periodontal diseases. J Am Dent Assoc. 2012;143(10 Suppl):6S-11S. doi:10.14219/jada.archive.2012.0341 

2. Abdulwahab M, Kamal M, Akbar A. Screening for high blood pressure at the dentist's office. Clin Cosmet Investig Dent. 2022;14:79-85. Published 2022 Apr 2. doi:10.2147/CCIDE.S358890 

3. Otero J, Guerrero M, Ortiz-Gomez Y. Blood pressure measurement in dental offices and dentists' cardiovascular risk management: A cross-sectional study. J Clin Exp Dent. 2025;17(7):e840-e847. doi:10.4317/jced.62888 

4. Goldman JS, Hahn SE, Catania JW, et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011;13(6):597-605. doi:10.1097/GIM.0b013e31821d69b8 

5. Belloy ME, Napolioni V, Greicius MD. A wuarter century of APOE and Alzheimer's disease: progress to date and the path forward. Neuron. 2019;101(5):820-838. doi:10.1016/j.neuron.2019.01.056 

6. Sims R, van der Lee SJ, Naj AC, et al. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet. 2017;49(9):1373-1384. doi:10.1038/ng.3916 

7. Wightman DP, Jansen IE, Savage JE, et al. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease. Nat Genet. 2021;53(9):1276-1282. doi:10.1038/s41588-021-00921-

8. Bellenguez C, Küçükali F, Jansen IE, et al. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nat Genet. 2022;54(4):412-436. doi:10.1038/s41588-022-01024-z

9. Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2020;324(8):772-781. doi:10.1001/jama.2020.12134 

10. Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19(5):422-433. doi:10.1016/S1474-4422(20)30071-5 

11. Ashton NJ, Pascoal TA, Karikari TK, et al. Plasma p-tau231: a new biomarker for incipient Alzheimer's disease pathology. Acta Neuropathol. 2021;141(5):709-724. doi:10.1007/s00401-021-02275-6

12. Teunissen CE, Verberk IMW, Thijssen EH, et al. Blood-based biomarkers for Alzheimer's disease: towards clinical implementation. Lancet Neurol. 2022;21(1):66-77. doi:10.1016/S1474-4422(21)00361-6 

13. Hampel H, Hu Y, Cummings J, et al. Blood-based biomarkers for Alzheimer's disease: current state and future use in a transformed global healthcare landscape. Neuron. 2023;111(18):2781-2799. doi:10.1016/j.neuron.2023.05.017

14. Mielke MM, Anderson M, Ashford JW, et al. Recommendations for clinical implementation of blood-based biomarkers for Alzheimer's disease. Alzheimers Dement. 2024;20(11):8216-8224. doi:10.1002/alz.14184