Ascending monoaminergic systems alterations in Alzheimer's disease. Translating basic science into clinical care
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- 作者：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
- 关键词：A¦Â ; amyloid ¦Â ; AADC ; L-amino acid decarboxylase ; ACC ; Anterior cingulate cortex ; AD ; Alzheimer's disease ; aMCI ; Amnestic mild cognitive impairment ; APP ; Amyloid precursor protein ; AR ; Adrenergic receptor ; ATMX ; atomoxetine ; BDNF ; Brain-derived neurotrop
- 刊名：Neuroscience and Biobehavioral Reviews
- 出版年：2013
- 出版时间：September, 2013
- 年：2013
- 卷：37
- 期：8
- 页码：1363-1379
- 全文大小：4119 K
文摘
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.