Biomarkers in Alzheimer's disease: new frontiers with olfactory models

Alzheimer's disease (AD), the leading cause of dementia worldwide, presents a significant diagnostic challenge, as clinical diagnoses are often made at advanced stages when neurodegenerative damage is already extensive. The study of biomarkers is necessary for improving identification, prognosis, and disease monitoring. Current research has primarily focused on cerebrospinal fluid and imaging biomarkers, including amyloid-β (Aβ1-42), phosphorylated tau, and total tau. However, these methods are invasive, expensive, and not widely accessible. Emerging approaches aim to identify novel, cost-effective, and minimally invasive biomarkers, particularly from blood-based and other peripheral sources. This review explores the role of olfactory neuronal precursors (ONPs) derived from the olfactory neuroepithelium (ONE) as a promising and innovative model for biomarker discovery in AD. ONPs can be non-invasively obtained directly from patients, offering a unique resource to study AD-related pathophysiological mechanisms. These neuronal lineage cells exhibit characteristics that make them a reliable surrogate model for central nervous system studies, enabling the evaluation of established biomarkers and facilitating the identification of novel candidates. Additionally, we discuss the potential of ONPs to enhance clinical practice through their accessibility and suitability for high-throughput biomarker analysis. By integrating the study of ONPs with existing biomarker research, this review highlights new frontiers in the quest to refine diagnostic tools and advance our understanding of Alzheimer's disease, paving the way for innovative strategies in early detection and personalized management.