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

Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring

Alain D. Dekker¹  Yannick Vermeiren¹  Debby Van Dam¹  Peter P. De Deyn¹  Juan Fortea²  Maria Carmona‐Iragui²  Alberto Lleó²  Rafael Blesa²  Sebastian Videla³  Laura Videla³  Susana Fernández³  Bessy Benejam³  Tony Aerts⁴  Anne Sieben⁴  Jean‐Jacques Martin⁴  Netherlands Brain Bank⁵  Ellen Gelpi⁶ 

[1] Department of Neurology and Alzheimer Research CenterUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands;Department of NeurologyHospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autonoma de BarcelonaBarcelonaSpain;Down Medical Center, Catalan Down Syndrome FoundationBarcelonaSpain;Laboratory of Neurochemistry and Behaviour, Institute Born‐Bunge, University of AntwerpWilrijkAntwerpBelgium;Netherlands Institute for NeuroscienceAmsterdamThe Netherlands;Neurological Tissue Bank—BiobancHospital Clinic Barcelona, Institut d'Investigacions Biomediques August Pi i SunyerBarcelonaSpain;

关键词: Alzheimer's disease;    Cerebrospinal fluid;    Dementia;    Dopamine;    Down syndrome;    Monoamines;   

DOI  :  10.1016/j.dadm.2017.11.001

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown