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

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-beta (A beta) isoforms might improve the AD versus non-AD differential diagnosis. Objective: To determine the added diagnostic value of A beta isoforms, A beta(1-37), A beta(1-38), and A beta(1-40), as compared to the AD CSF biomarkers A beta(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: A beta(1-37) and A beta(1-38) increased accuracy to differentiate AD from FTD or DLB. A beta(1-37), A beta(1-38), and A beta(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The A beta(1-42)/A beta(1-40) ratio improved diagnostic performance of A beta(1-42) in most differential diagnostic situations. A beta(1-42) levels were lower in APOE epsilon 4 carriers compared to non-carriers. Conclusions: A beta isoforms help to differentiate AD from FTD and DLB. A beta isoforms increase diagnostic performance of A beta(1-42). In contrast to A beta(1-42), A beta isoforms seem to be correlated with disease severity in AD. Adding the A beta isoforms to the current biomarker panel could enhance diagnostic accuracy.