Many pathogenic molecules underlying rare, mostly autosomal-dominant forms of Parkinsons disease have been identified. However, less is known about pathogenic pathways that lead to the common, 'sporadic' form. Now, Lewandowski et al. show that defects in the polyamine pathway are involved in the pathogenesis of Parkinsons disease. The authors focused on the brainstem as this region, particularly the dorsal motor nucleus of the vagus (DMNV), is thought to be affected early in the disease. Measuring cerebral blood volume using functional MRI provided high-resolution functional maps of the brainstems of human subjects. These showed that patients with Parkinsons disease had decreased cerebral blood volume in the DMNV, suggesting metabolic alterations in this region. By contrast, the inferior olivary nucleus (ION) - a neighbouring region - did not show such changes. Post-mortem analysis of Parkinson's disease brains also showed the DMNV to be positive for aggregates of the protein a-synuclein, which are associated with Parkinsons disease pathogenesis.
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