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Peer-reviewedCC BY 4.0Frontiers in Neurology

Longitudinal amyloid-beta measurements and blood–brain barrier dysfunction in cerebral amyloid angiopathy as part of the Mechanisms Of DEMentia project: protocol of the MODEM-LAMBDA-C study

  • Arno Stellingwerf1,2
  • Floris H. B. M. Schreuder1,2
  • H. Bea Kuiperij1,2
  • Anja G. Van Der Kolk3
  • Walter H. Backes4,5,6
  • Jurgen A. H. R. Claassen1,2,7,8
  • Marcel M. Verbeek1,2,9
9 affiliations
  1. 1Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre
  2. 2Radboud Alzheimer Centre, Radboud University Medical Centre
  3. 3Department of Medical Imaging, Radboudumc
  4. 4Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+
  5. 5Mental Health and Neuroscience (MHeNs) Research Institute, Maastricht University
  6. 6Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
  7. 7Department of Geriatric Medicine, Radboud University Medical Centre
  8. 8Department of Cardiovascular Sciences, University of Leicester
  9. 9Department of Human Genetics, Radboud University Medical Centre
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Abstract

Background: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta (Aβ) peptides within the cerebral vasculature and is a major cause of lobar intracerebral haemorrhage, cognitive impairment, and dementia. Vascular Aβ aggregates are enriched in shorter peptides (Aβ38 and Aβ40) whereas neuritic plaques, as observed in Alzheimer’s disease pathology, predominantly contain longer Aβ peptides (Aβ42 and Aβ43). These pathological signatures are reflected by reduced cerebrospinal fluid (CSF) Aβ levels. However, the longitudinal dynamics of CSF Aβ peptides in CAA and their relationship with blood–brain barrier (BBB) dysfunction remain poorly understood.

Methods: The MODEM-LAMBDA-C study is a longitudinal observational study including participants with CAA and age- and sex-matched control participants. At baseline, participants undergo clinical assessment, cognitive testing, blood pressure measurement, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the brain, blood sampling, and lumbar puncture to obtain CSF. At 2 years of follow-up, all assessments except MRI are repeated. Longitudinal changes in CSF Aβ peptide concentrations will be examined and related to cognitive performance, baseline MRI markers of cerebral small vessel disease and DCE-MRI-derived measures of BBB leakage. Additionally, CSF biomarkers of BBB dysfunction will be quantified and correlated with DCE-MRI markers of BBB dysfunction.

Conclusion: By integrating biochemical and imaging markers of Aβ pathology and BBB dysfunction, the MODEM-LAMBDA-C study aims to provide a comprehensive understanding of disease mechanisms underlying CAA, potentially contributing to improved diagnosis and prognostic strategies.

Clinical trial registration: https://onderzoekmetmensen.nl/en , identifier: NL85709.091.23.

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Cite

BibTeXRIS
BibTeX
@article{stellingwerf2026longitudinal,
  title = {{Longitudinal amyloid-beta measurements and blood–brain barrier dysfunction in cerebral amyloid angiopathy as part of the Mechanisms Of DEMentia project: protocol of the MODEM-LAMBDA-C study}},
  author = {Arno Stellingwerf and Floris H. B. M. Schreuder and H. Bea Kuiperij and Anja G. Van Der Kolk and Walter H. Backes and Jurgen A. H. R. Claassen and Marcel M. Verbeek},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1949765},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1949765/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Longitudinal amyloid-beta measurements and blood–brain barrier dysfunction in cerebral amyloid angiopathy as part of the Mechanisms Of DEMentia project: protocol of the MODEM-LAMBDA-C study
AU  - Arno Stellingwerf
AU  - Floris H. B. M. Schreuder
AU  - H. Bea Kuiperij
AU  - Anja G. Van Der Kolk
AU  - Walter H. Backes
AU  - Jurgen A. H. R. Claassen
AU  - Marcel M. Verbeek
PY  - 2026
DA  - 2026/10/28
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1949765
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1949765/full
AB  - Background: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta (Aβ) peptides within the cerebral vasculature and is a major cause of lobar intracerebral haemorrhage, cognitive impairment, and dementia. Vascular Aβ aggregates are enriched in shorter peptides (Aβ38 and Aβ40) whereas neuritic plaques, as observed in Alzheimer’s disease pathology, predominantly contain longer Aβ peptides (Aβ42 and Aβ43). These pathological signatures are reflected by reduced cerebrospinal fluid (CSF) Aβ levels. However, the longitudinal dynamics of CSF Aβ peptides in CAA and their relationship with blood–brain barrier (BBB) dysfunction remain poorly understood.  Methods: The MODEM-LAMBDA-C study is a longitudinal observational study including participants with CAA and age- and sex-matched control participants. At baseline, participants undergo clinical assessment, cognitive testing, blood pressure measurement, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the brain, blood sampling, and lumbar puncture to obtain CSF. At 2 years of follow-up, all assessments except MRI are repeated. Longitudinal changes in CSF Aβ peptide concentrations will be examined and related to cognitive performance, baseline MRI markers of cerebral small vessel disease and DCE-MRI-derived measures of BBB leakage. Additionally, CSF biomarkers of BBB dysfunction will be quantified and correlated with DCE-MRI markers of BBB dysfunction.  Conclusion: By integrating biochemical and imaging markers of Aβ pathology and BBB dysfunction, the MODEM-LAMBDA-C study aims to provide a comprehensive understanding of disease mechanisms underlying CAA, potentially contributing to improved diagnosis and prognostic strategies.  Clinical trial registration: https://onderzoekmetmensen.nl/en , identifier: NL85709.091.23.
SN  - 1664-2295
ER  -