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

doi:10.1016/j.neubiorev.2013.05.008

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

Division of Adult Acute Clinical

Research output: Contribution to journal › Review article › peer-review

176 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 language	English
Pages (from-to)	1363-1379
Number of pages	17
Journal	Neuroscience and Biobehavioral Reviews
Volume	37
Issue number	8
DOIs	https://doi.org/10.1016/j.neubiorev.2013.05.008
State	Published - Sep 2013

Keywords

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

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10.1016/j.neubiorev.2013.05.008

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

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.",

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

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

note = "Funding Information: This study was supported by grants from the Down Syndrome Research & Treatment Foundation (DSRTF), Research Down Syndrome (RDS) and the MIRECC and WRIISC programs at the VA Palo Alto Health Care System. We are very grateful to Ms. Persia Salehi for design and production of graphic work used in this study.",

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journal = "Neuroscience and Biobehavioral Reviews",

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T1 - Ascending monoaminergic systems alterations in Alzheimer's disease. Translating basic science into clinical care

AU - Trillo, Ludwig

AU - Das, Devsmita

AU - Hsieh, Wayne

AU - Medina, Brian

AU - Moghadam, Sarah

AU - Lin, Bill

AU - Dang, Van

AU - Sanchez, Martha Millan

AU - De Miguel, Zurine

AU - Ashford, J. Wesson

AU - Salehi, Ahmad

N1 - Funding Information: This study was supported by grants from the Down Syndrome Research & Treatment Foundation (DSRTF), Research Down Syndrome (RDS) and the MIRECC and WRIISC programs at the VA Palo Alto Health Care System. We are very grateful to Ms. Persia Salehi for design and production of graphic work used in this study.

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Cognition.

KW - Dopamine

KW - Down syndrome

KW - Histamine

KW - L-DOPS

KW - Locus coeruleus

KW - Norepinephrine

KW - Serotonin

KW - Single nucleotide polymorphism

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JO - Neuroscience and Biobehavioral Reviews

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ER -

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

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