Olfactory dysfunction, often the earliest symptom of Parkinson's disease (PD), can precede clinical diagnosis by over 20 years, yet its mechanism and link to α-synuclein pathology remain unclear. To understand the impact of α-synuclein pathology on the topographic olfactory sensory map that supports the detection and discrimination of particular odors, we created two double transgenic mouse models (α-Syn/M72 and α-Syn/P2) expressing tagged-M72 or tagged-P2 odor receptors in a human wild-type α-synuclein over-expressing background. We demonstrated that the sensory map is disrupted in these mice. Histological analysis showed a significant reduction in M72 and P2 olfactory sensory neurons (OSNs), with altered glomerular topographies as axons converged into supernumerary glomeruli of varying size and location. These findings suggest that α-synuclein overexpression impairs the mechanism guiding the convergence of OSN axons and thus formation of a precise olfactory sensory map. As OSNs in the nasal epithelium are accessible via non-invasive biopsy, they are a potential source of prodromal PD biomarkers.
Biju et al. (Tue,) studied this question.