Additional Value of CSF Amyloid-β 40 Levels in the Differentiation between FTLD and Control Subjects

Abstract

To determine the additional value of cerebrospinal fluid (CSF) amyloid-β_1-40 (Aβ₄₀) next to amyloid-β_1-42 (β₄₂), total tau (Tau), and tau phosphorylated at threonine-181 (pTau) to distinguish patients with frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and controls, we measured CSF levels of Aβ₄₀, Aβ₄₂, pTau, and Tau in 55 patients with FTLD, 60 with AD, and 40 control subjects. Logistic regression was used to identify biomarkers that best distinguished the groups. Additionally, a decision tree (cost=test method; Matlab 7.7) was used to predict diagnosis selecting the best set of biomarkers with the optimal cut-off. Logistic regression showed that Aβ₄₂ and pTau CSF levels provided optimal distinction between AD and FTLD. A combination of Aβ₄₂, Tau, and Aβ₄₀ optimally discriminated FTLD from controls and AD from controls. The decision tree used Aβ₄₂ (cut-off 578 pg/ml) to identify AD (positive predictive value (PPV) 97%), followed by Tau (cut-off 336 pg/ml) to identify FTLD (PPV 67%), and in the last step, Aβ₄₀ (cut-off 10 ng/ml) was used to differentiate controls (PPV 68%). Applying CSF Aβ₄₀ levels in the model, the PPV of diagnosis increased to 75% as opposed to 70% when only Aβ₄₂ and Tau were used. CSF Aβ₄₀ levels added to the conventional CSF biomarkers increases the potential to discriminate subjects with dementia from controls. Our findings favor the implementation of CSF Aβ₄₀ in differential diagnosis between FTLD, AD, and control subjects.