Olfactory Dysfunction as an Early Biomarker in Parkinson’s Disease

The presence of Lewy bodies in the substantia nigra is a pathological hallmark of PD. According to Braak staging, Lewy pathology begins in the olfactory bulb and dorsal motor nucleus of the vagus, consistent with the early onset of olfactory dysfunction [6]. Pathology then moves up the brainstem to involve the medulla and pontine tegmentum, and by Braak stage 3, it reaches the substantia nigra, at which point motor symptoms develop [8]. Further support for the olfactory bulb as a possible induction site for Lewy pathology comes from neuropathological studies examining brains of neurologically normal individuals who are found to have incidental Lewy bodies. Beach and colleagues found that when only one brain region was affected in those with incidental Lewy bodies, it was most commonly the olfactory bulb [9]. Lewy pathology in the olfactory bulb has also been shown to be 95% sensitive and 91% specific for identifying PD versus elderly controls, and accurately predicts the presence of pathology in other brain regions [10]. The synucleinopathy density scores in the olfactory bulb are correlated with UPDRS motor scores, suggesting that pathology develops early and continues to accumulate [10]