The Generative Brain
ISCIII Centro Nacional de Microbiologia, spongiform encephalopathies reference laboratory logo

ISCIII Centro Nacional de Microbiologia, spongiform encephalopathies reference laboratory

A laboratory of the Instituto de Salud Carlos III (ISCIII) in Madrid that runs the national premortem tests for suspected human prion disease in Spain: CSF 14-3-3 protein by western blot and PRNP gene sequencing from blood. In October 2020 it became the first Spanish laboratory accredited by ENAC under ISO 15189 for TSE testing in human samples, after more than 15 years of running the two tests. It serves public hospitals and regional public health labs under the EuroCJD surveillance frame and works alongside the national registry at the Centro Nacional de Epidemiologia. No RT-QuIC service is listed. Information only, not medical advice.

Key facts

  • In October 2020 ENAC accredited the ISCIII Centro Nacional de Microbiologia under UNE-EN ISO 15189 for TSE study in human samples, the first Spanish laboratory with this scope; the accreditation covers two premortem tests, CSF 14-3-3 protein and PRNP gene analysis from blood.
  • The two tests had been run at ISCIII for more than 15 years before accreditation, and the CNM had held accredited diagnostic activities since 2006.
  • The CNM clinical accreditation is ENAC 175/LE1213 under ISO 15189:2023, in force since 29 September 2006, with a scope revision dated 17 February 2026; the current scope lines for TSE tests were not checked.
  • The ISCIII service page lists 14-3-3 by SDS-PAGE western blot on at least 1 ml of CSF and PRNP by PCR and sequencing on 5 to 10 ml of EDTA blood, with informed consent required for the genetic study; samples travel at room temperature or 4 C, not frozen.
  • Requests come from public hospital services and regional public health laboratories; private laboratories, and requests with missing data, are handled through the CNM public price service portfolio.
  • The service is framed as molecular surveillance of suspected human TSE within the ECDC EuroCJD network, run with the Ministry of Health Directorate General of Public Health, under the 2001 notification order and Real Decreto 1940/2004 on zoonosis reference labs.
  • RT-QuIC is not listed among the laboratory's techniques. Nationally, RT-QuIC was used in only 31 percent of Spanish cases in 2024, and genetic studies and 14-3-3 analyses have fallen since 2017.
  • The ISCIII unit page gives the group three aims: molecular diagnosis, research on genetic susceptibility in Alzheimer and prion disease, and the molecular basis of conformational neurodegenerative diseases including CJD.
  • In 2020 the laboratory director was Miguel Calero, also described that year as responsible for the national reference centre for molecular diagnosis of human TSE at ISCIII.
  • Calero directed or co-directed UFIEC from June 2014, served as ISCIII deputy director for applied services from January 2021, and returned to UFIEC as research professor in January 2025.
  • The national registry relies on ISCIII labs: the 2021 Prion overview says genetic and 14-3-3 testing is done by a few EU validated labs at ISCIII and elsewhere, and the 2025 SEE abstract on variant CJD lists the CNM among its affiliations next to the CNE.
  • The label Spanish National Reference Center for CJD, ISCIII, used in the 2019 Neurology age at onset paper, is assigned to both a CNE registry epidemiologist and Calero, so it describes a joint ISCIII function rather than this laboratory alone.
  • The group contributes to international genetics: Calero coauthored the 2024 GWAS of 3,773 sporadic CJD cases, which found PRNP codon 129 the main modifier of survival, and the 2025 Brain multiomic study that tied STX6 and PDIA4 to sporadic CJD risk.
  • A 2009 European study of CSF from 174 genetic TSE patients, with Calero among Spanish coauthors, found biomarker positivity of 81 percent in genetic CJD but 13 percent in FFI and 10 percent in GSS.

Timeline

  1. 2006ENAC accreditation 175/LE1213 of the CNM clinical laboratory comes into force.
  2. 2009European study of CSF biomarkers in genetic TSE, with ISS Rome as lead and Spanish coauthors including Calero, published.
  3. 2014Calero starts directing or co-directing UFIEC.
  4. 2019Neurology age at onset paper credits the Spanish National Reference Center for CJD, ISCIII, to a CNE epidemiologist and Calero.
  5. 2020Calero described as responsible for the national reference centre for molecular diagnosis of human TSE.
  6. 2020ENAC ISO 15189 accreditation for CSF 14-3-3 and PRNP testing announced.
  7. 2021Calero moves to ISCIII deputy director for applied services, training and research.
  8. 2024Sporadic CJD GWAS with Calero as coauthor published.
  9. 2025Calero returns to UFIEC as research professor.
  10. 2025SEE abstract on variant CJD surveillance lists the CNM with the CNE; Brain multiomic CJD risk gene study published.
  11. 2026ENAC scope revision 20 of accreditation 175/LE1213.
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