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

Paolo Calabresi, Davide Chiasserini, Leonardo Biscetti, Paolo Eusebi, Nicola Salvadori, Giulia Frattini, Simone Simoni, Naomi De Roeck, Nicola Tambasco, Erik Stoops, Hugo Vanderstichele, Sebastiaan Engelborghs, Brit Mollenhauer, Lucilla Parnetti

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background: Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB) share clinical and molecular features. Cerebrospinal fluid (CSF) biomarkers may help the characterization of these diseases, improving the differential diagnosis. We evaluated the diagnostic performance of five CSF biomarkers across a well-characterized cohort of patients diagnosed with AD, DLB, PDD, and Parkinson's disease (PD). Methods: A total of 208 patients were enrolled in 3 European centers. The diagnostic groups (AD, n = 48; DLB, n = 40; PDD, n = 20; PD, n = 54) were compared with cognitively healthy neurological control subjects (patients with other neurological diseases [OND], n = 46). CSF levels of fatty acid binding protein 3, heart type (FABP3), α-synuclein (α-syn), amyloid-β peptide 1-42, total tau (t-tau), and phosphorylated tau 181 (p-tau) were assessed with immunoassays. Univariate and multivariate statistical analyses were applied to calculate the diagnostic value of the biomarkers as well as their association with clinical scores. Results: FABP3 levels were significantly increased in patients with AD and DLB compared with those with PD and OND (p < 0.001). CSF t-tau, p-tau, and α-syn were significantly higher in patients with AD than in patients with PDD, DLB, PD, and OND. Combination of FABP3 with p-tau showed high accuracy for the differential diagnosis between AD and DLB (AUC 0.92), whereas patients with AD were separated from those with PDD using a combination of p-tau, FABP3, and α-syn (AUC 0.96). CSF FABP3 was inversely associated with Mini Mental State Examination score in the whole cohort (r = -0.42, p < 0.001). Conclusions: The combination of CSF biomarkers linked to different aspects of neurodegeneration, such as FABP3, α-syn, and AD biomarkers, improves the biochemical characterization of AD and Lewy body disorders.
Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalALZHEIMER'S RESEARCH &amp; THERAPY
Volume9
DOIs
Publication statusPublished - 2017

Keywords

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Amyloid
  • Amyloid beta-Peptides
  • Area Under Curve
  • Biomarkers
  • Cerebrospinal fluid
  • Dementia
  • Diagnosis, Differential
  • Europe
  • Fatty Acid Binding Protein 3
  • Female
  • Heart fatty acid binding protein
  • Humans
  • Immunoassay
  • Lewy Body Disease
  • Male
  • Mental Status and Dementia Tests
  • Middle Aged
  • Parkinson Disease
  • Peptide Fragments
  • Sex Factors
  • Statistics as Topic
  • Supranuclear Palsy, Progressive
  • Tau
  • alpha-Synuclein
  • tau Proteins
  • α-Synuclein

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