Additional Value of CSF Amyloid-β40 Levels in the Differentiation between FTLD and Control Subjects

To determine the additional value of cerebrospinal fluid (CSF) amyloid-beta(1-40) (A beta(40)) next to amyloid-beta(1-42) (A beta(42)), 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 A beta(40), A beta(42), 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 A beta(42) and pTau CSF levels provided optimal distinction between AD and FTLD. A combination of A beta(42), Tau, and A beta(40) optimally discriminated FTLD from controls and AD from controls. The decision tree used A beta(42) (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, A beta(40) (cut-off 10 ng/ml) was used to differentiate controls (PPV 68%). Applying CSF A beta(40) levels in the model, the PPV of diagnosis increased to 75% as opposed to 70% when only A beta(42) and Tau were used. CSF A beta(40) levels added to the conventional CSF biomarkers increases the potential to discriminate subjects with dementia from controls. Our findings favor the implementation of CSF A beta(40) in differential diagnosis between FTLD, AD, and control subjects.