DIFFERENTIAL ROLE OF CSF FATTY ACID BINDING PROTEIN 3, α-SYNUCLEIN AND ALZHEIMER’S DISEASE CORE BIOMARKERS IN LEWY BODY DISORDERS AND ALZHEIMER’S DEMENTIA

Abstract

Accumulation, in extra- or intracellular deposits, of aggregated and misfolded proteins characterizes Alzheimer disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). This reflects in an overlapping of clinical presentations, especially between AD and DLB. Here we evaluated the diagnostic performance of a panel of five cerebrospinal fluid (CSF) biomarkers in a cohort of patients diagnosed with AD, DLB, PDD and Parkinson's disease (PD). Here we measured CSF levels of fatty acid binding protein (FABP3), α-synuclein (α-syn) and classical AD biomarkers in a large cohort of patients diagnosed with PD (n= 54), AD (n=48), DLB (n=40), PDD (n=20) and control subjects (n=46). ELISA immunoassays were used to assess CSF levels of fatty acid binding protein (FABP3), α-synuclein (α-syn), amyloid β 1–42 (Aβ1–42), total tau (t-tau) and phosphorylated tau 181 (p-tau). Univariate and multivariate statistical analyses were applied to calculate the diagnostic performance of the five CSF biomarkers, as well as their association with clinical parameters. CSF t-tau, p-tau and α-syn levels were significantly higher in AD than in PDD, DLB, PD patients and controls. CSF FABP3 levels were significantly increased in AD and DLB patients compared to PD and controls (p<0.001). A combination of FABP3 and p-tau reached an optimal accuracy for discriminating AD and DLB (AUC=0.92), while the best performance for distinguishing AD and PDD was obtained using a combination of p-tau, FABP3 and α-syn (AUC = 0.96). CSF FABP3 levels were inversely associated with Mini Mental State Examination scores in the whole cohort (r = -0.42, p < 0.001). No correlation was found between CSF biomarkers and motor scores (UPDRS-III and H&Y). The combination of CSF biomarkers linked to different aspects of neurodegeneration may improve the differential diagnosis of neurodegenerative disorders. In this context FABP3 plays a key role when combined to CSF AD core biomarkers and α-synuclein.