Serum MHPG strongly predicts conversion to Alzheimer's disease in behaviorally characterized subjects with Down syndrome.

Autor:	Dekker AD; Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium., Coppus AM; Dichterbij, Center for the Intellectually Disabled, Gennep, The Netherlands Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, The Netherlands., Vermeiren Y; Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium., Aerts T; Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium., van Duijn CM; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands., Kremer BP; Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Naudé PJ; Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Van Dam D; Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium., De Deyn PP; Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium.
Jazyk:	angličtina
Zdroj:	Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2015; Vol. 43 (3), pp. 871-91.
DOI:	10.3233/JAD-140783
Abstrakt:	Background: Down syndrome (DS) is the most prevalent genetic cause of intellectual disability. Early-onset Alzheimer's disease (AD) frequently develops in DS and is characterized by progressive memory loss and behavioral and psychological signs and symptoms of dementia (BPSD). Predicting and monitoring the progression of AD in DS is necessary to enable adaptive caretaking. Objective: Reliable blood biomarkers that aid the prediction of AD are necessary, since cerebrospinal fluid sampling is rather burdensome, particularly for people with DS. Here, we investigate serum levels of eight biogenic amines and their metabolites in relation to dementia staging and probable BPSD items. Methods: Using RP-HPLC with electrochemical detection, (nor)adrenergic (NA/A and MHPG), serotonergic (5-HT and 5-HIAA), and dopaminergic (DA, HVA, and DOPAC) compounds were quantified in the serum of DS subjects with established AD at baseline (n = 51), DS subjects without AD (n = 50), non-demented DS individuals that converted to AD over time (n = 50), and, finally, healthy non-DS controls (n = 22). Results: Serum MHPG levels were significantly lower in demented and converted DS subjects (p < 0.0001) compared to non-demented DS individuals and healthy controls. Those subjects with MHPG levels below median had a more than tenfold increased risk of developing dementia. Furthermore, significant correlations were observed between monoaminergic serum values and various probable BPSD items within each DS group. Conclusion: Decreased serum MHPG levels show great potential as biomarker to monitor and predict conversion to AD in DS. Moreover, significant monoaminergic alterations related to probable BPSD items, suggesting that monoaminergic dysregulation is an underlying biological mechanism, and demonstrating the need to develop a validated rating scale for BPSD in DS.
Databáze:	MEDLINE
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