Cognitive Impairment in Alzheimer’s Disease: Targeting the Histaminergic System

Alzheimer’s disease is a neurodegenerative disease character ized by a progressive decline in cognitive functions and in the ability to continue activities of daily living. The exact causes of Alzheimer’s disease are yet unknown, but researchers suggest that the formation and aggregation of β-amyloid and phos phorylated tau plaques are among the well-known factors that explain the pathophysiogenesis of the disease. The mechanisms by which β-amyloid leads to cognitive decline in Alzheimer’s disease are associated with degeneration in both cholinergic and glutamatergic neurotransmission. However, it is proposed that different neurotransmitter systems with neuronal hista mine also participate in the progress and continuance of cog nitive deficits associated with Alzheimer’s disease. Histamine serves as a neurotransmitter in brain. Histamine-containing neurons in the brain are concentrated mainly in tuberomammil lary nucleus located posterior to the hypothalamus and project widely to the regions such as the cerebellum and hippocampus that are related to memory and cognitive functions. The cog nitive function modulated by histamine is thanks to the effect of 4 metabotropic receptors: H1, H2, H3, and H4. Pathological changes in histamine level and histamine receptor expression in patients with Alzheimer’s disease are largely predictive of ensuing cognitive deficits. The review gives a synopsis of the functions of histaminergic neurotransmission in Alzheimer’s disease-related cognitive decline, as well as the effects of H1, H2, H3, and H4 on animal and clinical researches.