Olfactory-Cleft Biopsy in Alzheimer's Disease: An Emerging Neuroimmune Window into Preclinical Pathobiology
James Chmiel1, Aleksandra Kładna2
1Faculty of Physical Culture and Health, Institute of Physical Culture Sciences, University of Szczecin, Al. Piastów 40B Block 6, 71-065 Szczecin, Poland.
Abstract:
Olfactory dysfunction is an early non-cognitive feature of Alzheimer's disease (AD), but smell impairment has traditionally been used mainly as a behavioral marker. This review examines the emerging use of the olfactory cleft as an accessible source of living neuronal, epithelial, progenitor, and immune cells for studying AD pathobiology. Histopathological and patient-derived culture studies have reported amyloid-β, tau, oxidative-stress, mitochondrial, biometal, and transcriptional abnormalities in olfactory tissue. More recent endoscopically guided brush sampling with single-cell profiling has identified activated memory CD8 T-cell states, inflammatory myeloid programs, and neuronal metabolic changes, including in cognitively unimpaired individuals with abnormal cerebrospinal-fluid amyloid biomarkers. These findings support olfactory-cleft sampling as a research platform for investigating early neural-immune changes, but current evidence is based on small, largely cross-sectional cohorts and does not establish disease specificity, causality, or prognostic utility. Longitudinal multicenter studies integrating olfactory-tissue profiling with established fluid, imaging, genetic, cognitive, and olfactory biomarkers are required before clinical translation.
Related Concept Videos
Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Alzheimer Disease ll: Pathophysiology
Dementia l: Introduction
Alzheimer Disease l: Introduction


