The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson's disease:: a critical analysis of α-synuclein staging

Aims: It has been proposed that alpha-synuclein (alpha Syn) pathology in Parkinson's disease (PD) spreads in a predictable caudo-rostral way with the earliest changes seen in the dorsal motor nucleus of the vagus nerve (DMV). However, the reliability of this stereotypical spread of alpha Syn pathology has been questioned. In addition, the comparative occurrence of alpha Syn pathology in the spinal cord and brain has not been closely studied. Methods: In order to address these issues, we have examined 71 cases of PD from the UK Parkinson's Disease Society Tissue Bank at Imperial College, London. The incidence and topographic distribution of alpha Syn pathology in several brain regions and the spinal cord were assessed. Results: The most affected regions were the substantia nigra (SN; in 100% of cases) followed by the Nucleus Basalis of Meynert (NBM) in 98.5%. Fifty-three per cent of cases showed a distribution pattern of alpha Syn compatible with a caudo-rostral spread of alpha Syn through the PD brain. However, 47% of the cases did not fit the predicted spread of alpha Syn pathology and in 7% the DMV was not affected even though alpha Syn inclusions were found in SN and cortical regions. We also observed a high incidence of alpha Syn in the spinal cord with concomitant affection of the DMV and in a few cases in the absence of DMV involvement. Conclusions: Our results demonstrate a predominant involvement of the SN and NBM in PD but do not support the existence of a medullary induction site of alpha Syn pathology in all PD brains.