The expression of alpha-, beta-, and gamma-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases

A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown , alpha-synuclein has been implicated in synaptic plasticity associated wit h avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common fea ture of these disorders and the olfactory receptor neurons (ORNs) of the ol factory epithelium (OE) regenerate throughout the lifespan, we used antibod ies specific for alpha-, beta-, and gamma-synucleins to examine the olfacto ry mucosa of patients with PD, DLB, AD, MSA, and controls without a neurolo gical disorder. Although antibodies to alpha- and beta-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative d isorders, similar pathology was also seen in the OE of controls. More signi ficantly, we show here for the first time that alpha-, beta-, and gamma-syn ucleins are differentially expressed in cells of the OE and respiratory epi thelium and that alpha-synuclein is the most abundant synuclein in the olfa ctory mucosa, where it is prominently expressed in ORNs. Moreover, alpha- a nd gamma-synucleins also were prominent in the OE basal cells, which includ e the progenitor cells of the ORNs in the OE. Thus, our data on synuclein e xpression within the OE may signify that synuclein plays a role in the rege neration and plasticity of ORNs in the adult human OE. (C) 1999 Academic Pr ess.