Monoaminergic neuropathology in Alzheimer's disease

Simic, Goran, Leko, Mirjana Babic, Wray, Selina, Harrington, Charles R., Delalle, Ivana, Jovanov-Milosevic, Natasa, Bazadona, Danira, Buee, Luc, de Silva, Rohan, Di Giovanni, Giuseppe, Wischik, Claude M. and Hof, Patrick R. 2017. Monoaminergic neuropathology in Alzheimer's disease. Progress in Neurobiology 151 , pp. 101-138. 10.1016/j.pneurobio.2016.04.001

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	0301-0082
Date of Acceptance:	5 April 2016
Last Modified:	03 Sep 2019 09:17
URI:	https://orca.cardiff.ac.uk/id/eprint/110521

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