Ascending monoaminergic systems alterations in Alzheimer's disease. Translating basic science into clinical care

Ludwig Trillo, Devsmita Das, Wayne Hsieh, Brian Medina, Sarah Moghadam, Bill Lin, Van Dang, Martha Millan Sanchez, Zurine De Miguel, J. Wesson Ashford, Ahmad Salehi

Research output: Contribution to journalReview articlepeer-review

125 Scopus citations

Abstract

Extensive neuropathological studies have established a compelling link between abnormalities in structure and function of subcortical monoaminergic (MA-ergic) systems and the pathophysiology of Alzheimer's disease (AD). The main cell populations of these systems including the locus coeruleus, the raphe nuclei, and the tuberomamillary nucleus undergo significant degeneration in AD, thereby depriving the hippocampal and cortical neurons from their critical modulatory influence. These studies have been complemented by genome wide association studies linking polymorphisms in key genes involved in the MA-ergic systems and particular behavioral abnormalities in AD. Importantly, several recent studies have shown that improvement of the MA-ergic systems can both restore cognitive function and reduce AD-related pathology in animal models of neurodegeneration. This review aims to explore the link between abnormalities in the MA-ergic systems and AD symptomatology as well as the therapeutic strategies targeting these systems. Furthermore, we will examine possible mechanisms behind basic vulnerability of MA-ergic neurons in AD.

Original languageEnglish
Pages (from-to)1363-1379
Number of pages17
JournalNeuroscience and Biobehavioral Reviews
Volume37
Issue number8
DOIs
StatePublished - Sep 2013

Keywords

  • Alzheimer's disease
  • Cognition.
  • Dopamine
  • Down syndrome
  • Histamine
  • L-DOPS
  • Locus coeruleus
  • Norepinephrine
  • Serotonin
  • Single nucleotide polymorphism

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