Inverse relationship between brain noradrenaline level and dopamine loss in Parkinson disease: a possible neuroprotective role for noradrenaline.

BACKGROUND Experimental findings using animal models of Parkinson disease (PD) suggest that noradrenaline might protect dopamine neurons from damage. OBJECTIVE To assess whether human brain regions having high levels of noradrenaline are less susceptible to dopamine loss in PD. DESIGN Case-control study. SETTING Postmortem investigation. PARTICIPANTS Autopsied brains of patients with PD and of healthy control subjects. Main Outcomes Measures We compared the extent of dopamine loss in different regions relative to levels of noradrenaline found in healthy brain, with special attention devoted to the dopamine-rich nucleus accumbens, which has noradrenaline-rich and noradrenaline-poor subdivisions. RESULTS Among 20 brain areas, dopamine loss in PD was negatively correlated with healthy noradrenaline levels (r = 0.83), with regions rich in noradrenaline (eg, the noradrenaline-rich portion of the nucleus accumbens) spared from dopamine loss. However, within the striatum, noradrenaline levels in the caudate and putamen were similar, despite dopamine's being more markedly reduced in the putamen. CONCLUSIONS Our postmortem data are consistent with animal findings suggesting that noradrenaline might affect dopamine neuron loss in PD and that a noradrenergic approach (although not aimed at the as yet unknown primary cause of PD) could be neuroprotective. This possibility should also be considered when noradrenergic therapy is provided for symptomatic purposes in PD.