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

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-beta (A beta)(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 A beta(1-42) 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/A beta(1-42) ratio (cut-off = 0.7). A significant correlation between HFABP/A beta(1-42) ratio and MMSE annual decrease rate was also documented (p < 0.0001). HFABP/A beta(1-42) ratio might be a useful predictor of conversion in MCI patients.