title: Serum MHPG strongly predicts conversion to Alzheimer's disease in behaviorally characterized subjects with Down syndrome.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Alain D
authors.initials: AD
authors.lastname: Dekker
authors.affiliation: 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.
authors.forename: Antonia M W
authors.initials: AM
authors.lastname: Coppus
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Vermeiren
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium.
authors.forename: Tony
authors.initials: T
authors.lastname: Aerts
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Berry P
authors.initials: BP
authors.lastname: Kremer
authors.affiliation: Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Pieter J W
authors.initials: PJ
authors.lastname: Naudé
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Wilrijk, Antwerp, Belgium.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
authors.affiliation: 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.
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004298:Dopamine / Q000097:blood; D004314:Down Syndrome / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000097:blood*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D008734:Methoxyhydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine
keywords: Alzheimer's disease; Down syndrome; MHPG; RP-HPLC; behavioral and psychological signs and symptoms of dementia (BPSD); biogenic amines; biomarkers