title: Monoaminergic neuropathology in Alzheimer's disease.
abstract: None of the proposed mechanisms of Alzheimer's disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5-20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia. Electronic address: gsimic@hiim.hr.
authors.forename: Goran
authors.initials: G
authors.lastname: Šimić
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Babić Leko
authors.affiliation: Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Selina
authors.initials: S
authors.lastname: Wray
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Harrington
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Delalle
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Jovanov-Milošević
authors.affiliation: Department of Neurology, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Danira
authors.initials: D
authors.lastname: Bažadona
authors.affiliation: University of Lille, Inserm, CHU-Lille, UMR-S 1172, Alzheimer & Tauopathies, Lille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.affiliation: Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
authors.forename: Claude M
authors.initials: CM
authors.lastname: Wischik
authors.affiliation: Fishberg Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D006801:Humans; D000069338:Neuropathology; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D016875:tau Proteins
keywords: 5-hydroxytryptamine (serotonin); Alzheimer’s disease; Amyloid beta (Aβ) peptide; Blood-brain barrier; Cerebrospinal fluid; Epigenetics; Locus coeruleus; Metals; Monoamines; Neurofibrillary degeneration; Non-cognitive symptoms; Nucleus raphe dorsalis; Phosphorylation; Sleep-wake cycle; Tau protein