CSF Levels of Heart Fatty Acid Binding Protein are Altered During Early Phases of Alzheimer's Disease

Article type: Research Article

Authors: Chiasserini, Davide^{a; c; 1; *} | Parnetti, Lucilla^{a; 1; *} | Andreasson, Ulf^b | Zetterberg, Henrik^b | Giannandrea, David^a | Calabresi, Paolo^{a; c} | Blennow, Kaj^b

Affiliations: [a] Clinica Neurologica, Ospedale S. Maria della Misericordia, Università di Perugia, Perugia, Italy | [b] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [c] Fondazione S. Lucia, I.R.C.C.S. Rome, Italy

Correspondence: [*] Correspondence to: Davide Chiasserini, Ph.D., Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, 06132 Perugia, Italy. Tel.: +39 075 585 5813; Fax: +39 075 585 5814; E-mail: [email protected]; Lucilla Parnetti MD, Ph.D., Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, 06132 Perugia, Italy. Tel.: +39 075 578 3545; Fax: +39 075 578 3621; E-mail: [email protected].

Note: [1] Both authors contributed equally to this work.

Note: [] Handling Associate Editor: Barbara Borroni

Abstract: Heart fatty acid binding protein (HFABP) has been proposed as a putative marker for dementia disorders. To evaluate the value of this protein as an early marker of Alzheimer's disease (AD), we analyzed HFABP level and the classical biomarkers amyloid-β (Aβ)1–42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) followed up for four years (n = 41), AD (n = 32), and subjects with other neurological diseases without dementia (OND, n = 25). HFABP levels were higher in AD patients and in MCI converting to AD (MCI-AD) with respect to OND and to cognitively stable MCI patients (MCI-MCI). The receiver operator characteristics analysis for HFABP alone showed a sensitivity of 87% and a specificity of 81% for AD versus OND (area under the curve, AUC = 0.83); sensitivity and specificity were 46% and 94%, respectively, when comparing MCI-MCI versus MCI-AD. CSF HFABP levels showed a strong positive correlation with both t-tau and p-tau. Interestingly, the ratio between HFABP and Aβ1–42 improved the performance in distinguishing AD from OND (sensitivity: 90%; specificity 82%, AUC = 0.89), and gave the best accuracy in discriminating MCI-AD from MCI-MCI (sensitivity: 80%; specificity 100%, AUC = 0.90). Survival analysis by means of Kaplan-Meier curve showed a significantly higher proportion of MCI patients converting to AD in the group with higher values of HFABP/Aβ1–42 ratio (cut-off = 0.7). A significant correlation between HFABP/Aβ1–42 ratio and MMSE annual decrease rate was also documented (p < 0.0001). HFABP/Aβ1–42 ratio might be a useful predictor of conversion in MCI patients.

Keywords: Alzheimer's disease, amyloid-β_1–42, biomarkers, cerebrospinal fluid, mild cognitive impairment, heart fatty acid binding protein, phosphorylated tau, total-tau

DOI: 10.3233/JAD-2010-101293

Journal: Journal of Alzheimer's Disease, vol. 22, no. 4, pp. 1281-1288, 2010