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

Article type: Research Article

Authors: Struyfs, Hannea; 1 | Van Broeck, Biancab; 1 | Timmers, Maartenc | Fransen, Erikd | Sleegers, Kristele; f | Van Broeckhoven, Christinee; f | De Deyn, Peter P.a; g; h | Streffer, Johannes R.c | Mercken, Marcb | Engelborghs, Sebastiaana; g; *

Affiliations: [a] Reference Center for Biological Markers of Dementia (BIODEM), and Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [b] Janssen Research and Development, Neuroscience Discovery, Beerse, Belgium | [c] Janssen Research and Development, Experimental Medicine Neuroscience, Beerse, Belgium | [d] StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium | [e] Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium | [f] Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [g] Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium | [h] Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, The Netherlands

Correspondence: [*] Correspondence to: Prof. Dr. Sebastiaan Engelborghs, University of Antwerp, Reference Center for Biological Markers of Dementia (BIODEM), Universiteitsplein 1, 2610 Antwerp, Belgium. Tel.: +32 3 265 23 94; Fax: +32 3 265 26 18; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Keywords: Alzheimer's disease, amyloid, biological markers, cerebrospinal fluid, diagnosis, differential, mild cognitive impairment

DOI: 10.3233/JAD-141986

Journal: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 813-822, 2015

Accepted 29 December 2014
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Published: 24 March 2015
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Supplementary Materials:

Supplementary Tables.

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, Aβ1-37, Aβ1-38, and Aβ1-40, as compared to the AD CSF biomarkers Aβ1-42, T-tau, and P-tau181P.

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:

Aβ1-37 and Aβ1-38 increased accuracy to differentiate AD from FTD or DLB. Aβ1-37, Aβ1-38, and Aβ1-40 levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ1-42/Aβ1-40 ratio improved diagnostic performance of Aβ1-42 in most differential diagnostic situations. Aβ1-42 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 Aβ1-42. 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.

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