title: Neuronal histamine and cognitive symptoms in Alzheimer's disease.
abstract: Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. This article is part of a Special Issue entitled 'Histamine Receptors'.
authors.affiliation: Mental Health Research and Treatment Center, Ruhr University Bochum, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Zlomuzica
authors.affiliation: Center for Psychological Consultation and Psychotherapy, Georg-August University Göttingen, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Dere
authors.affiliation: Institute for Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Binder
authors.affiliation: Institute of Experimental Psychology, Center for Behavioral Neuroscience, Heinrich-Heine University of Düsseldorf, Germany.
authors.forename: Maria Angelica
authors.initials: MA
authors.lastname: De Souza Silva
authors.affiliation: Institute of Experimental Psychology, Center for Behavioral Neuroscience, Heinrich-Heine University of Düsseldorf, Germany.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Huston
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; UFR des Sciences de la Vie (927), Université Pierre et Marie Curie Paris 6, France. Electronic address: dere@em.mpg.de.
authors.forename: Ekrem
authors.initials: E
authors.lastname: Dere
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*
chemical_list: D006632:Histamine
keywords: Dementia; Episodic-like memory; Histamine receptor knockout mice; Histamine receptors