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

Article type: Research Article

Authors: Verwey, Nicolaas A.^{a; b; *} | Kester, Maartje I.^a | van der Flier, Wiesje M.^{a; c} | Veerhuis, Robert^{b; d} | Berkhof, Hans^c | Twaalfhoven, Harry^b | Blankenstein, Marinus A.^b | Scheltens and, Philip^a | Pijnenburg, Yolande A.L.^a

Affiliations: [a] Department of Neurology, VU University Medical Center, Alzheimer Center Amsterdam, The Netherlands | [b] Department of Clinical Chemistry, VU University Medical Center, Alzheimer Center Amsterdam, The Netherlands | [c] Department of Epidemiology and Biostatistcs, VU University Medical Center, Alzheimer Center Amsterdam, The Netherlands | [d] Department Psychiatry, VU University Medical Center, Alzheimer Center Amsterdam, The Netherlands

Correspondence: [*] Corresponding to: Mr. N.A. Verwey, MD, Department Clinical Chemistry, VU University Medical Center, P.O. BOX 7057, 1007 MB, Amsterdam, The Netherlands. Tel.: +31 20 4443868; Fax: +31 20 4443895; E-mail: [email protected].

Abstract: To determine the additional value of cerebrospinal fluid (CSF) amyloid-β1-40 (Aβ40) next to amyloid-β1-42 (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.

Keywords: Alzheimer's disease, amyloid-β, biomarker, cerebrospinal fluid, ELISA, frontotemporal lobar degeneration

DOI: 10.3233/JAD-2010-1392

Journal: Journal of Alzheimer's Disease, vol. 20, no. 2, pp. 445-452, 2010