Diagnosis of cerebral amyloid angiopathy relies on criteria based on MRI markers. However, these are based on late and indirect markers and do not provide definitive proof of disease. This hampers early diagnosis. Thus, novel biomarkers are needed. Cerebrospinal fluid biomarkers are a proven option.read more
Background Cerebral Amyloid Angiopathy
What is CAA?CAA is an important cause of cognitive decline or dementia and of cerebral hemorrhages in old age. It has a high prevalence (an estimated 10-50% of the general population), which increases with age. Also, approximately 80% of Alzheimer’s disease patients have CAA, the extent of which may vary considerably.
How does CAA develop?The normal transport of amyloid β out of the brain parenchyma, across the so-called blood-brain barrier, towards the blood seems to be impaired. As a consequence, the amyloid β protein accumulates in the vessels of the brain. Once clinical symptoms become evident, CAA is already widespread in the brain, but at that time intervention is likely too late. Therefore, so-called biomarkers ('alarm signals') of early CAA development are clearly needed to improve early diagnosis and to stimulate the development of effective treatments.
How to detect CAA?Currently, the definitive diagnosis of CAA can only be made by postmortem analysis of the brain tissue. Sensitive and specific diagnostic tests that allow detecting CAA during life are therefore dearly needed to allow for earlier detection and possible interventions.
Figure 1: Example of typical MRI finding indicative of CAA: lobar microbleeds. The arrow indicates a lobar microbleed (SWI sequence).
Figure 2: Immunohistochemical demonstration of amyloid β protein in CAA (anti-amyloid β staining).
Start and end date
- Start date: 1 April 2018
- End date: 1 April 2022
Diagnosis of cerebral amyloid angiopathy (CAA) currently relies on the 'Boston criteria', which are based on MRI markers. However, these criteria are based on late and indirect hemorrhagic markers of CAA and do not provide definitive proof of the disease; this hampers early diagnosis.read more
Recently, a transgenic rat model of CAA was developed that closely resembles human CAA deposition in the microvasculature. This model allows for studying disease progression in relation to biomarker levels longitudinally, and gives the opportunity to investigate prodromal stages of disease.read more
This project aims to identify a profile of amyloid β-peptides in cerebrospinal fluid that is specific for CAA. If we manage to establish a CAA-specific profile of amyloid β peptide, this offers new possibilities for (early) diagnosis of CAA and monitoring the progression of the disease.read more
External partner Leiden University Medical Center
Marieke Wermer PhD and Gisela Terwindt PhD.
External partner ADx Neurosciences
Hugo VanderStichele PhD.
External partner University of Gothenburg
Erik Portelius PhD.
External partner The University of Rhode Island
William E. Van Nostrand PhD.