Relationship between β-Secretase, Inflammation and Core Cerebrospinal Fluid Biomarkers for Alzheimer's Disease

Daniel Alcolea, María Carmona-Iragui, Marc Suárez-Calvet, M. Belén Sánchez-Saudinós, Isabel Sala, Sofía Antón-Aguirre, Rafael Blesa, Jordi Clarimón, Juan Fortea, Alberto Lleó

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91 Citations (Scopus)


© 2014 - IOS Press and the authors. All rights reserved. Background: Biomarkers in the cerebrospinal fluid (CSF) can track specific pathophysiological pathways underlying Alzheimer's disease (AD). The connection between these biomarkers remains unclear. Objective: To study six CSF biomarkers in a clinical cohort of patients with different neurodegenerative conditions. Methods: We measured markers of amyloid-β protein precursor (AβPP) processing (Aβ42, sAβPPβ, β-secretase activity), neuronal damage (total tau, p-tau), and inflammation (YKL-40) in CSF from 194 participants with the following diagnoses: subjective cognitive impairment or non-amnestic mild cognitive impairment (na-SCI, n = 44), amnestic mild cognitive impairment (aMCI, n = 45), dementia of the Alzheimer type (DAT, n = 59), frontotemporal dementia (FTD, n = 22), and 24 cognitively normal controls. We compared biomarkers between clinical groups and CSF-profile groups, and we analyzed the correlation between biomarkers. Results: CSF levels of sAβPPβ were decreased in FTD patients compared to the other groups. YKL-40 was elevated in DAT and FTD, and also in aMCI patients. CSF Aβ42 correlated positively with β-secretase activity (RS = 0.262) and sAβPPβ (RS = 0.341). CSF YKL-40 correlated positively with total tau (RS = 0.467) and p-tau (RS = 0.429). CSF p-tau and sAβPPβ contributed significantly to distinguish DAT from FTD. Conclusions: CSF biomarkers of AβPP processing correlate with each other and are decreased in FTD. The inflammatory marker YKL-40 is increased in different neurodegenerative diseases, even in early stages, and it correlates with biomarkers of neurodegeneration. This suggests that inflammation is a common feature in AD and FTD. A combination of CSF biomarkers tracking distinct pathophysiological processes may be useful to classify subjects with neurodegenerative conditions.
Original languageEnglish
Pages (from-to)157-167
JournalJournal of Alzheimer's Disease
Issue number1
Publication statusPublished - 1 Jan 2014


  • Alzheimer's disease
  • amyloid-β protein precursor
  • biological markers
  • cerebrospinal fluid
  • frontotemporal dementia
  • inflammation
  • YKL-40
  • β-secretase


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