Leiden University Scholarly Publications

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Koemans, E.A. (2024)

Staging cerebral amyloid angiopathy: from marker to model

Doctoral Thesis
Cerebral Amyloid Angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH) in the elderly, and affects millions of people worldwide. CAA is caused by the deposition of the protein Amyloid-β in the walls of the cerebral and leptomeningeal vessels, which leads to vessel fragility and eventually rupture. CAA has a variable disease course and can present with a spectrum of symptoms. There is currently no cure for CAA, and certain diagnosis during life remains challenging.
This thesis has used data from patients with hereditary and non-hereditary (sporadic) CAA to investigate novel clinical and radiological (MRI) markers of CAA, and has used them to formulate a pathophysiologic framework for the temporal ordering of disease processes in CAA. Our results provide new insights in the disease cascade, can aid in diagnosing the disease and have important implications for future clinical trial design, aiding in the identification and timing of candidates for disease...Show moreCerebral Amyloid Angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH) in the elderly, and affects millions of people worldwide. CAA is caused by the deposition of the protein Amyloid-β in the walls of the cerebral and leptomeningeal vessels, which leads to vessel fragility and eventually rupture. CAA has a variable disease course and can present with a spectrum of symptoms. There is currently no cure for CAA, and certain diagnosis during life remains challenging.
This thesis has used data from patients with hereditary and non-hereditary (sporadic) CAA to investigate novel clinical and radiological (MRI) markers of CAA, and has used them to formulate a pathophysiologic framework for the temporal ordering of disease processes in CAA. Our results provide new insights in the disease cascade, can aid in diagnosing the disease and have important implications for future clinical trial design, aiding in the identification and timing of candidates for disease-modifying treatments and the choice for the appropriate biomarkers to monitor treatment effect. CAA is a disease with a complex disease cascade and a large variety in disease course, both clinically and radiologically. However, it is just this variety that gives hope for the future: if we find what drives variability in CAA we might find ways for disease modification, prevention and treatment, and identification of in vivo biomarkers with specificity for CAA are a vital part of this search.
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Cerebral amyloid angiopathy
Dutch-type cerebral amyloid angiopathy
Intracerebral hemorrhage
MRI
Biomarker
All authors
Koemans, E.A.
Supervisor
Wermer, M.J.H.; Terwindt, G.M.
Co-supervisor
Walderveen, M.A.A. van
Committee
Roon-Mom, W.M.C. van; Verbeek, M.M.; Biessels, G.J.; Kruit, M.C.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2024-05-29
ISBN (print)
9789083359731

Funding

Sponsorship
The research projects in this thesis were supported by grants from the Dutch Heart Foundation (grant no. 2016T086) and the Dutch CAA Foundation.Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged.