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

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.