Isonaka R, et al. - Because alpha-synuclein (AS) deposition within sympathetic neurons has been proposed as a link between neurogenic orthostatic hypotension (nOH) and cardiac noradrenergic deficiency observed in Lewy body diseases, researchers sought to validate methodology to quantify AS colocalization with tyrosine hydroxylase (TH), as well as evaluate the links of AS/TH colocalization with myocardial norepinephrine content and cardiac sympathetic neuroimaging data in nOH. In four Lewy body and three rare non-Lewy body nOH patients, they assessed postmortem sympathetic ganglionic AS/TH colocalization indices and myocardial norepinephrine contents. In vivo skin biopsies and thoracic ¹⁸F-dopamine positron emission tomographic scanning were performed on 16 Lewy body and 11 non-Lewy body nOH patients. Findings revealed an association of AS deposition in sympathetic noradrenergic nerves, with postmortem neurochemical and in vivo neuroimaging evidence of myocardial noradrenergic deficiency in Lewy body nOH. This was indicative of a pathophysiological role of intraneuronal AS deposition in the myocardial sympathetic neurodegeneration attending Lewy body nOH.