title: Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis.
abstract: BACKGROUND
  Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis.
  
  
  OBJECTIVE
  To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P).
  
  
  METHODS
  CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD (n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16).
  
  
  RESULTS
  Aβ(1-37) and Aβ(1-38) increased accuracy to differentiate AD from FTD or DLB. Aβ(1-37), Aβ(1-38), and Aβ(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ(1-42)/Aβ(1-40) ratio improved diagnostic performance of Aβ(1-42) in most differential diagnostic situations. Aβ(1-42) levels were lower in APOE ε4 carriers compared to non-carriers.
  
  
  CONCLUSIONS
  Aβ isoforms help to differentiate AD from FTD and DLB. Aβ isoforms increase diagnostic performance of Aβ(1-42). In contrast to Aβ1-42, Aβ isoforms seem to be correlated with disease severity in AD. Adding the Aβ isoforms to the current biomarker panel could enhance diagnostic accuracy.
authors: Reference Center for Biological Markers of Dementia (BIODEM), and Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors: Hanne
authors: H
authors: Struyfs
authors: Janssen Research and Development, Neuroscience Discovery, Beerse, Belgium.
authors: Bianca
authors: B
authors: Van Broeck
authors: Janssen Research and Development, Experimental Medicine Neuroscience, Beerse, Belgium.
authors: Maarten
authors: M
authors: Timmers
authors: StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium.
authors: Erik
authors: E
authors: Fransen
authors: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors: Kristel
authors: K
authors: Sleegers
authors: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors: Christine
authors: C
authors: Van Broeckhoven
authors: Reference Center for Biological Markers of Dementia (BIODEM), and Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, The Netherlands.
authors: Peter P
authors: PP
authors: De Deyn
authors: Janssen Research and Development, Experimental Medicine Neuroscience, Beerse, Belgium.
authors: Johannes R
authors: JR
authors: Streffer
authors: Janssen Research and Development, Neuroscience Discovery, Beerse, Belgium.
authors: Marc
authors: M
authors: Mercken
authors: Reference Center for Biological Markers of Dementia (BIODEM), and Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
authors: Sebastiaan
authors: S
authors: Engelborghs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D020033:Protein Isoforms / Q000134:cerebrospinal fluid*; D012372:ROC Curve; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D020033:Protein Isoforms; D016875:tau Proteins
keywords: Alzheimer's disease; amyloid; biological markers; cerebrospinal fluid; diagnosis; differential; mild cognitive impairment