TLRs and NLRs modulate oral microbiome involvement in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the most common and irreversible type of dementia, accounting for more than half of all dementia cases. Early diagnosis of AD plays a role in slowing the progression of the disease and also preserving the quality of life of patients. However, there is often a time lag of several decades between the biological onset of the disease and the time of clinical diagnosis. At the time of diagnosis, the patient often has noticeable cognitive decline, which reduces the effectiveness of available treatments. This diagnostic time lag from onset to the onset of symptoms highlights the need to identify accessible and cost-effective screening tools, such as biomarker-based diagnostic and screening methods. Studies have implicated disorders of the oral-brain axis in the pathogenesis of neurodegenerative diseases such as AD. Oral dysbiosis has been epidemiologically associated with an increased risk of cognitive decline and AD, making the oral microbiome a potential biomarker for screening and early diagnosis of AD. Oral dysbiosis also plays a role in the pathogenesis of AD by increasing systemic inflammation and neuroinflammation. TLR/NLR signaling has been identified as a key intrinsic pathway in the pathogenesis of these neuroinflammations and systemic inflammation, which may suggest the use of inhibitors such as TAK-242/MCC950 as a potential therapeutic approach in the treatment of AD, although preclinical and clinical evidence for the use of these inhibitors in the course of AD is still very limited. In this review, we discuss oral dysbiosis in AD and review studies investigating the mouth-brain axis as an effective pathway in AD from diagnosis to treatment. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.