Histamine-N-methyltransferase (HMT) inactivates the neurotransmitter histamine. 
Central histaminergic deficits may contribute to the cognitive impairment of 
neurodegenerative disorders including Alzheimer's disease (AD) and Down syndrome 
(DS). However, there is no evidence for histaminergic deficits in Pick's disease 
(PiD). HMT levels were measured in the frontal cortex and cerebellum of brains 
of patients with AD, DS, and PiD, and normal aged subjects using proteomics 
techniques. In frontal cortex, HMT was significantly decreased in DS, but 
significantly increased in PiD compared with controls. HMT levels were 
comparable in cerebellum of all groups. Elevated HMT in PiD could lead to 
increased histamine degradation that in turn would be in agreement with impaired 
cognitive functions of PiD. Decreased HMT in DS would be compatible with 
findings of decreased histamine synthesis, thus reflecting a compensation 
mechanism to antagonize reduced synthesis by decreased degradation.