2026-04-13T04:59:34Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4300882026-03-13T04:56:43Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Dekker, Alain D. author Vermeiren, Yannick author Carmona Iragui, Maria author Benejam, Bessy author Videla Toro, Laura author Gelpi, Ellen author Aerts, Tony author Van Dam, Debby author Fernández, Susana author Lleó, Alberto author Videla, Sebastián author Sieben, Anne author Martin, Jean-Jacques author Blesa, Rafael author Fortea, Juan author De Deyn, Peter Paul author Universitat Autònoma de Barcelona author 2017 Altres ajuts: Fundacio Bancaria La Caixa, Marató de TV3 (20141210), Grifols Foundation, Generalitat de Catalunya 2014SGR-0235,Fundació Catalana de Sındrome de Down (FCSD), Interuniversity Poles of Attraction of the Belgian Federal Science Policy Office/IAP P7/16, Belgian Foundation for Alzheimer Research/SAO-FRA 15002. 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. 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). 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. 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. Alzheimer's disease Cerebrospinal fluid Dementia Dopamine Down syndrome Monoamines MHPG Neurotransmitter Noradrenaline Plasma Serotonin Trisomy 21 Monoaminergic impairment in Down syndrome with Alzheimer's disease compared to early-onset Alzheimer's disease