NEURONAL HISTAMINE DEFICIT IN ALZHEIMERS-DISEASE

Histamine is known to be a neurotransmitter in the brain, but it has n ot been clearly implicated in major diseases. AII histaminergic neuron s reside in the posterior hypothalamus and innervate most brain areas, which is compatible with the concept that histamine is involved in ge neral central regulatory mechanisms. A sensitive high-performance liqu id chromatographic fluorimetric method was used to measure histamine c ontents 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 histamin e content was significantly reduced in the hypothalamus (42% of contro l value), hippocampus (43%) and temporal cortex (53%) of Alzheimer bra ins. 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 Alzheime r brains and controls. No histamine-containing mast cells were seen in these temporal structures. Histamine in the human temporal lobe is st ored in nerve fibers originating from the posterior hypothalamus, and not in mast cells. Decrease in brain histamine may contribute to the c ognitive decline in Alzheimer's disease directly or through the cholin ergic system. Development of drugs that penetrate the blood-brain barr ier and increase histaminergic activity might be beneficial in Alzheim er's disease. (C) 1997 IBRO. Published by Elsevier Science Ltd.