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Pregled bibliografske jedinice broj: 810136

Rad u postupku objavljivanja

Autori: Šimić, Goran; Babić Leko, Mirjana; Wray, Selina; Harrington, Charles; Delalle, Ivana; Jovanov-Milošević, Nataša; Bažadona, Danira; Buée, Luc; de Silva, Rohan; Di Giovanni, Giuseppe; Wischik, Claude; Hof, Patrick R.
Naslov: Monoaminergic Neuropathology in Alzheimer's disease
Izvornik: Progress in neurobiology (0301-0082) (2016)
Status rada: prihvaćen
Ključne riječi: 5-hydroxytryptamine (serotonin); Alzheimer's disease; amyloid beta (Aβ) protein; blood-brain barrier; cerebrospinal fluid; epigenetics; locus coeruleus; metals; monoamines; neurofibrillary degeneration; non-cognitive symptoms; nucleus raphe dorsalis; phosphorylation; sleep-wake cycle; tau protein
Sažetak:
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.
Projekt / tema: IP-2014-09-9730, HRZZ-09/16, 108-1081870-1942
Izvorni jezik: ENG
Kategorija: Znanstveni
Znanstvena područja:
Temeljne medicinske znanosti
Tiskani medij: da
Upisao u CROSBI: Goran Šimić (gsimic@hiim.hr), 18. Tra. 2016. u 12:08 sati



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