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Monoaminergic neuropathology in Alzheimer's disease

Simic, G; Leko, MB; Wray, S; Harrington, CR; Delalle, I; Jovanov-Milosevic, N; Bazadona, D; ... Hof, PR; + view all (2016) Monoaminergic neuropathology in Alzheimer's disease. Progress in Neurobiology , 151 pp. 101-138. 10.1016/j.pneurobio.2016.04.001. Green open access

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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.

Type: Article
Title: Monoaminergic neuropathology in Alzheimer's disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.pneurobio.2016.04.001
Publisher version: https://doi.org/10.1016/j.pneurobio.2016.04.001
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, 5-hydroxytryptamine (serotonin), Alzheimer's disease, Amyloid beta (A beta) 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, MILD COGNITIVE IMPAIRMENT, CEREBRAL AMYLOID ANGIOPATHY, TRANSGENIC MOUSE MODEL, DORSAL RAPHE NUCLEUS, PLACEBO-CONTROLLED TRIAL, H-3 RECEPTOR ANTAGONIST, CENTRAL-NERVOUS-SYSTEM, PROGRESSIVE SUPRANUCLEAR PALSY, ARGYROPHILIC GRAIN DISEASE, DOPAMINE-BETA-HYDROXYLASE
URI: http://discovery.ucl.ac.uk/id/eprint/10055854
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