Year: 2024
Type: review
Abstract: We recently proposed a new disease model of Parkinson's disease - the a-Synuclein Origin site and Connectome model. The model posits that the initial pathology starts either in the olfactory bulb or amygdala leading to a brain-first subtype, or in the enteric nervous system leading to a body-first subtype. These subtypes should be distinguishable early in the disease course on a range of imaging, clinical, and neuropathological markers. Here, we review recent original human studies, which tested the predictions of the model. Molecular imaging studies were generally in agreement with the model, whereas structural imaging studies, such as MRI volumetry, showed conflicting findings. Most large-scale clinical studies were supportive, reporting clustering of relevant markers of the body-first subtype, including REM-sleep behavior disorder, constipation, autonomic dysfunction, neuropsychiatric symptoms, and cognitive impairment. Finally, studies of a-synuclein deposition in antemortem and postmortem tissues revealed distribution of pathology, which generally supports the model.
Source: Parkinsonism & Related Disorders
Authors: Jacob Horsager, Per Borghammer
Institutions: Aarhus University Hospital, Aarhus University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,630
Funders: Lundbeckfonden, H. Lundbeck A/S
Awards: G5442934107, G640838616
OpenAlex ID: W4392858331