2. Academic Validation
  3. Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis

Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis

  • J Alzheimers Dis. 2015;45(3):813-22. doi: 10.3233/JAD-141986.
Hanne Struyfs 1,  Bianca Van Broeck 2,  Maarten Timmers 3,  Erik Fransen 4,  Kristel Sleegers 5,  Christine Van Broeckhoven 5,  Peter P De Deyn 6,  Johannes R Streffer 3,  Marc Mercken 2,  Sebastiaan Engelborghs 7
Affiliations

Affiliations

  • 1 Reference Center for Biological Markers of Dementia (BIODEM), and Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
  • 2 Janssen Research and Development, Neuroscience Discovery, Beerse, Belgium.
  • 3 Janssen Research and Development, Experimental Medicine Neuroscience, Beerse, Belgium.
  • 4 StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium.
  • 5 Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
  • 6 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.
  • 7 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.
PMID: 25633670 DOI: 10.3233/JAD-141986
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.

Keywords

Alzheimer's disease; amyloid; biological markers; cerebrospinal fluid; diagnosis; differential; mild cognitive impairment.

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