This review proposes a "dual-hit" hypothesis for the aetiology of sporadic Parkinson's disease (PD), suggesting that the disease begins with a neurotropic pathogen, likely viral, entering the brain through two routes: nasal and gastric. The nasal route involves anterograde progression into the temporal lobe, while the gastric route involves secondary swallowing of nasal secretions in saliva, which may contain the pathogen. After penetrating the epithelial lining, the pathogen could enter axons of the Meissner's plexus. The dual-hit hypothesis is supported by evidence of early involvement of the olfactory bulb and enteric plexus in PD, as well as the presence of Lewy bodies in these regions. The pathogen may then spread retrogradely through the vagus nerve to the medulla and eventually reach the substantia nigra, where typical aspects of PD commence. The review also discusses evidence for olfactory and autonomic dysfunction in PD, including studies showing impaired smell function in PD patients and in presymptomatic individuals. It also highlights the role of autonomic dysfunction, such as dysphagia and gastrointestinal disorders, in PD. The review concludes that the most parsimonious explanation for the initial events of sporadic PD is pathogenic access to the brain through the stomach and nose, hence the term "dual-hit." The review also discusses the pathological process underlying sporadic PD, including the development of α-synuclein-containing inclusion bodies in the form of Lewy bodies in perikarya and Lewy neurites in neuronal processes. The review highlights the involvement of the olfactory system and autonomic systems in the early stages of PD, which develop prior to the onset of classical somatomotor symptoms. The review also discusses the role of viral infection in PD, including evidence of viral entry through the nasal and gastric routes, and the potential for viral pathogens to initiate autoimmune responses. The review concludes that the dual-hit hypothesis provides a plausible explanation for the early involvement of the olfactory and enteric systems in PD, and the subsequent spread of pathology to other regions of the brain.This review proposes a "dual-hit" hypothesis for the aetiology of sporadic Parkinson's disease (PD), suggesting that the disease begins with a neurotropic pathogen, likely viral, entering the brain through two routes: nasal and gastric. The nasal route involves anterograde progression into the temporal lobe, while the gastric route involves secondary swallowing of nasal secretions in saliva, which may contain the pathogen. After penetrating the epithelial lining, the pathogen could enter axons of the Meissner's plexus. The dual-hit hypothesis is supported by evidence of early involvement of the olfactory bulb and enteric plexus in PD, as well as the presence of Lewy bodies in these regions. The pathogen may then spread retrogradely through the vagus nerve to the medulla and eventually reach the substantia nigra, where typical aspects of PD commence. The review also discusses evidence for olfactory and autonomic dysfunction in PD, including studies showing impaired smell function in PD patients and in presymptomatic individuals. It also highlights the role of autonomic dysfunction, such as dysphagia and gastrointestinal disorders, in PD. The review concludes that the most parsimonious explanation for the initial events of sporadic PD is pathogenic access to the brain through the stomach and nose, hence the term "dual-hit." The review also discusses the pathological process underlying sporadic PD, including the development of α-synuclein-containing inclusion bodies in the form of Lewy bodies in perikarya and Lewy neurites in neuronal processes. The review highlights the involvement of the olfactory system and autonomic systems in the early stages of PD, which develop prior to the onset of classical somatomotor symptoms. The review also discusses the role of viral infection in PD, including evidence of viral entry through the nasal and gastric routes, and the potential for viral pathogens to initiate autoimmune responses. The review concludes that the dual-hit hypothesis provides a plausible explanation for the early involvement of the olfactory and enteric systems in PD, and the subsequent spread of pathology to other regions of the brain.