Histaminergic tuberomammillary neuron loss in multiple system atrophy and dementia with Lewy bodies

Background: Histaminergic neurons of the tuberomammillary nucleus are critical for maintenance of wakefulness and participate in basal ganglia modulation and sympathoexcitation. All of these functions are affected in multiple system atrophy and dementia with Lewy bodies. Objectives: To determine the involvement of histaminergic neurons in these synucleinopathies. Methods: Immunocytochemical staining for histidine decarboxylase and stereological cell counts in the posterolateral hypothalamus from six cases with multiple system atrophy, six with dementia with Lewy bodies, and five healthy controls. Results: Compared with healthy controls, significant reduction of histaminergic neurons was found both in multiple system atrophy (total estimated cell count, 94,677 ± 5,521 vs. 169,579 ± 12,443; P < 0.001) and in dementia with Lewy bodies (91,110 ± 13,021 vs. 169,579 ± 12,443; P < 0.001). Conclusions: Loss of tuberomammillary histaminergic neurons could potentially contribute to motor, sleep, and autonomic manifestations of both multiple system atrophy and dementia with Lewy bodies.