Biomarkers for early detection of Parkinson disease

There are approximately 1,000 genes involved in odor recognition and 347 that code for functional receptors. This enables our distinguishing of approximately 4,000–10,000 distinct odorous ligands, a scientific discovery that earned a Nobel Prize in 2004.¹ The olfactory nerve (CN1) contains 6–10 million receptor cells whose ciliated dendrites and cell bodies are contained within a specialized (neuro)epithelium located within the posterior nasal cavity (figure).² These olfactory receptor cells are interspersed with sustentacular cells for stability of the epithelium and basal cells (stem cells) that provide a regenerative capacity. Also in residence are the Bowman glands, which secrete and maintain the mucous layer upon the cilia that float just beneath the (neuro)epithelium. This mucous contains several proteins that may help metabolize xenobiotics and support epithelial integrity (e.g., mucin, lysozyme, amylase, immunoglobulin G).² Once an odorant enters the nose, it interacts with the receptors located on the surface of the olfactory cilia and a chemical signature generates a crescendo of action potentials in the olfactory neuron axon (figure). These project to higher brain regions involved in conscious thought processes and the limbic system, generating the emotional, motivational, and memory context.³ Olfactory dysfunction presenting as hyposmia impairs the satisfaction gained from foods and inhibits the detection of environmental hazards (e.g., toxins, fire, spoiled foods, and natural gas leaks). Diminished olfactory inputs also dampen the neural/cephalic phase of digestion responsible for stimulating exocrine secretions in the mouth (e.g., amylase), stomach (e.g., hydrochloric acid, digestive enzymes), and small intestine (e.g., lipase).^4,5 These secretions facilitate the absorption and assimilation of micronutrients and fatty acids and contribute to the nature of the microbiome in the host by governing the gut pH.⁶