Dataset Information

Monoaminergic impairment in Down syndrome with Alzheimer's disease compared to early-onset Alzheimer's disease.

ABSTRACT:

Introduction

People with Down syndrome (DS) are at high risk for Alzheimer's disease (AD). Defects in monoamine neurotransmitter systems are implicated in DS and AD but have not been comprehensively studied in DS.

Methods

Noradrenaline, adrenaline, and their metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; and serotonin and its metabolite 5-hydroxyindoleacetic acid were quantified in 15 brain regions of DS without AD (DS, n = 4), DS with AD (DS+AD, n = 17), early-onset AD (EOAD, n = 11) patients, and healthy non-DS controls (n = 10) in the general population. Moreover, monoaminergic concentrations were determined in cerebrospinal fluid (CSF)/plasma samples of DS (n = 37/149), DS with prodromal AD (DS+pAD, n = 13/36), and DS+AD (n = 18/40).

Results

In brain, noradrenergic and serotonergic compounds were overall reduced in DS+AD versus EOAD, while the dopaminergic system showed a bidirectional change. For DS versus non-DS controls, significantly decreased MHPG levels were noted in various brain regions, though to a lesser extent than for DS+AD versus EOAD. Apart from DOPAC, CSF/plasma concentrations were not altered between groups.

Discussion

Monoamine neurotransmitters and metabolites were evidently impacted in DS, DS+AD, and EOAD. DS and DS+AD presented a remarkably similar monoaminergic profile, possibly related to early deposition of amyloid pathology in DS. To confirm whether monoaminergic alterations are indeed due to early amyloid β accumulation, future avenues include positron emission tomography studies of monoaminergic neurotransmission in relation to amyloid deposition, as well as relating monoaminergic concentrations to CSF/plasma levels of amyloid β and tau within individuals.

SUBMITTER: Dekker AD

PROVIDER: S-EPMC5956808 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Monoaminergic impairment in Down syndrome with Alzheimer's disease compared to early-onset Alzheimer's disease.

Dekker Alain D AD Vermeiren Yannick Y Carmona-Iragui Maria M Benejam Bessy B Videla Laura L Gelpi Ellen E Aerts Tony T Van Dam Debby D Fernández Susana S Lleó Alberto A Videla Sebastian S Sieben Anne A Martin Jean-Jacques JJ Blesa Rafael R Fortea Juan J De Deyn Peter P PP

Alzheimer's & dementia (Amsterdam, Netherlands) 20171123

<h4>Introduction</h4>People with Down syndrome (DS) are at high risk for Alzheimer's disease (AD). Defects in monoamine neurotransmitter systems are implicated in DS and AD but have not been comprehensively studied in DS.<h4>Methods</h4>Noradrenaline, adrenaline, and their metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; and serotonin and its metabolite 5-hydroxyindoleacetic acid were quantified in 15 br ...[more]

PMID: 29780859

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Dataset Information

Monoaminergic impairment in Down syndrome with Alzheimer's disease compared to early-onset Alzheimer's disease.

Introduction

Methods

Results

Discussion

Publications

Monoaminergic impairment in Down syndrome with Alzheimer's disease compared to early-onset Alzheimer's disease.

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