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COMBINATION OF CEREBROSPINAL FLUID H-FABP AND CORE ALZHEIMER'S DISEASE BIOMARKERS IMPROVES THE DIFFERENTIAL DIAGNOSIS OF NEURODEGENERATIVE DISORDERS

      Background

      Heart fatty acid binding protein (H-FABP) has been proposed as cerebrospinal fluid (CSF) neurodegeneration biomarker. Consistently, increased CSF H-FABP levels were found in Alzheimer’s Disease (AD) and Dementia with Lewy Bodies (DLB) compared to controls [1,2]. Moreover, in mild cognitive impairment (MCI) and in Parkinson’s disease (PD), high CSF H-FABP levels were associated with cognitive decline [1,3]. Here, we measured CSF H-FABP levels together with the core AD biomarkers - Aβ1-42 (Aβ42), total tau protein (t-tau), phosphorylated tau 181 (p-tau) - in a large cohort of well characterized patients with different neurodegenerative disorders, including: AD (n=48), Parkinson’s disease (PD, n=54), Dementia with Lewy Bodies (DLB, n=40), Parkinson Disease with Dementia (PDD, n=21) and other neurological disorders (OND, n=47) as controls. Our aim was to determine the accuracy of CSF H-FABP levels in distinguishing patients with AD from other conditions.

      Methods

      A total of 210 patients were recruited from three different European centers: the University Hospital of Perugia (n=151), the BIODEM lab, University of Antwerp (n=20), and the University Medical Center, Gottingen (n=40). CSF H-FABP, Aβ42, t-tau and p-tau levels were measured with ELISA immunoassays.

      Results

      CSF H-FABP levels were significantly higher in AD and DLB patients compared to PD and controls; a similar trend was observed in the PDD group .CSF t-tau levels were significantly increased in AD as compared to PDD, DLB, PD and controls. CSF H-FABP significantly correlated with CSF t-tau levels (r=0.64, p<0.001). CSF H-FABP/t-tau ratio showed a high accuracy for differential diagnosis between AD and DLB (AUC=0.92, specificity 83%, sensitivity 88%) and between AD and PDD (AUC=0.97, specificity 89%, sensitivity 95%). H-FABP showed an inverse correlation with cognitive decline, as assessed with Mini Mental Status Examination (r = -0.41, p<0.001).

      Conclusions

      CSF H-FABP can be considered a neurodegeneration biomarker possibly linked to the development of dementia. The combination of H-FABP with the core AD CSF biomarkers may help to improve the differential diagnosis of dementia disorders. [1] Chiasserini, D. et al., J. Alzheimers. Dis. 2010;22(4):1281-8. [2] Mollenhauer, B. et al., 2007, 02115, 366–375. [3] Backstrom DC et al., Jama Neur.2015 Oct; 72 (10): 1175-82.
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