Neuronal histamine deficit in Alzheimer's disease

Histamine is known to be a neurotransmitter in the brain, but it has not been clearly implicated in major diseases. All histaminergic neurons reside in the posterior hypothalamus and innervate most brain areas, which is compatible with the concept that histamine is involved in general central regulatory mechanisms. A sensitive high-performance liquid chromatographic fluorimetric method was used to measure histamine contents in post mortem Alzheimer brains and age-matched controls. The cellular storage sites and distribution of histaminergic nerve fibers were examined with a specific immunohistochemical method. The histamine content was significantly reduced in the hypothalamus (42% of control value), hippocampus (43%) and temporal cortex (53%) of Alzheimer brains. Differences in other cortical areas, putamen and substantia nigra were not significant. Histamine-containing nerve fibers were found in the hippocampus, parahippocampal gyrus and subiculum of both Alzheimer brains and controls. No histamine-containing mast cells were seen in these temporal structures. Histamine in the human temporal lobe is stored in nerve fibers originating from the posterior hypothalamus, and not in mast cells. Decrease in brain histamine may contribute to the cognitive decline in Alzheimer's disease directly or through the cholinergic system. Development of drugs that penetrate the blood brain barrier and increase histaminergic activity might be beneficial in Alzheimer's disease.