Is congenital anosmia protective for Parkinson’s disease triggered by pathogenic entrance through the nose?

The prevalence of smell loss in Parkinson’s Disease (PD) patients greatly exceeds that of the characteristic motor symptoms defining the disease by several years. One hypothesis of the cause of PD states that it is initiated in the olfactory bulb — the critical first central processing stage of the olfactory system — and that the olfactory nerve might serve as an entry point to the OB for pathogens or environmental components. But what if there was no OB to start with? Recent data demonstrate that cortical, but not peripheral, blindness acts as a protective factor against schizophrenia and other psychotic disorders. We hypothesize that individuals with the rare diagnose Isolated Congential Anosmia (ICA) are immune to PD given that they are born without OBs. If true, it would strongly support the theory that PD might start in the bulb. However, if one could identify even one single PD patient with an established ICA diagnosis with non-existing OBs, a so-called black swan, this would effectively falsify the hypothesis. In this commentary, we model the likely occurrence of such potential comorbidity and we postulate that it is possible to find this black swan; a finding that would falsify a salient hypothesis within the PD research community.