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, 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.