Better biomarkers needed for CAA Quarter of over-55s have CAA but diagnosis is difficult to establish

CAA (cerebral amyloid angiopathy) is a relatively unknown brain disease that occurs mostly in the elderly. About a quarter of people over 55 have the condition, according to doctoral research by Anna de Kort at the Radboudumc. Better biomarkers are needed for faster and proper diagnosis.

Cerebral amyloid angiopathy (CAA) is caused by accumulation of the amyloid-beta protein in small blood vessels of the cerebral cortex, the outermost part of the brain. As a result, the blood vessels become more fragile and begin to function less well, increasing the risk of brain hemorrhage and cognitive impairment such as problems with memory, language, attention, concentration and orientation. CAA is relatively common. Research by Anna de Kort indicates that about a quarter of all elderly people have CAA, although only a small proportion of people actually have symptoms.

Better biomarkers needed

CAA is diagnosed with an MRI scan that shows the suspected effects of CAA. About a quarter of people over 55 have CAA, but only 7 percent of this age group see signs of it on an MRI. So in a large proportion of people with CAA in the brain tissue, CAA is missed. That's why De Kort started looking for possible biomarkers; for substances in brain fluid or blood that are very specific to the condition. Such biomarkers are important in making a correct diagnosis of the disorder. Such a biomarker is also useful in drug research. If a potential new drug is effective, it is likely to affect the concentration of the biomarker. De Kort investigated neuroleukin and platelet-derived-growth-factor-receptor-β, but these do not appear to be suitable biomarkers for CAA. In contrast, the composition of various forms of amyloid-β in cerebrospinal fluid does appear to be a potential biomarker for CAA.

CAA and Alzheimer's disease

Alzheimer's and CAA often occur together. Not entirely unexpected, since both involve the accumulation of the protein amyloid-β. In Alzheimer's, the protein accumulates between nerve cells; in CAA, the accumulation takes place in the wall of small blood vessels. De Kort showed that about half of people with Alzheimer's have moderate to severe CAA pathology. This is an important finding. De Kort: "In the United States and other countries, despite much criticism and doubts from the scientific community, new drugs against Alzheimer's have recently become available. Apart from its effect in Alzheimer's, this anti-Aβ immunotherapy in people with CAA gives a greatly increased risk of getting serious side effects such as brain swelling and brain bleeding. New cerebrospinal fluid biomarkers for CAA may help determine whether people with Alzheimer's disease also have CAA. This will make it easier to determine for whom the drug is safe."

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Anna de Kort received her PhD from Radboudumc/ Radboud University on April 17 for the study "New cerebrospinal fluid biomarkers can improve diagnosis of cerebral amyloid angiopathy.

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