Cerebral Amyloid Angiopathy (CAA)
Cerebral Amyloid Angiopathy (CAA) is a degenerative neurovascular disease characterized by the deposition of beta-amyloid within the walls of small to medium-sized blood vessels of the cerebral cortex and leptomeninges. This process leads to vascular fragility, which increases the risk of lobar intracerebral hemorrhages, microbleeds, and cognitive decline. CAA is particularly frequent in the elderly and often coexists with Alzheimer’s disease.
CAA is caused by the accumulation of beta-amyloid (the Aβ1-40 isoform) in cerebral vessels—an isoform different from the one that deposits in the parenchymal plaques of Alzheimer’s disease. There are sporadic forms of CAA (the most common) and rare hereditary forms with autosomal dominant transmission. Apolipoprotein E, particularly the ε4 allele, is associated with a higher risk of developing the disease and increased pathological severity.
CAA can remain asymptomatic for years, but it clinically presents with:
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Spontaneous lobar intracerebral hemorrhages, typically recurrent and most frequently localized in the occipital, temporal, or parietal lobes.
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Progressive cognitive decline, even in the absence of typical Alzheimer’s markers.
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Seizures or Transient Focal Neurological Episodes (TFNE)—transient neurological events similar to TIAs (Transient Ischemic Attacks).
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Headaches, mental confusion, or focal deficits in the presence of associated edema (inflammatory forms of CAA).
Definitive diagnosis requires histopathological examination; however, in clinical practice, clinico-radiological criteria (Boston Criteria) are used. The primary tools include:
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Brain MRI with T2-GRE and SWI sequences* to detect microbleeds, lobar hemorrhages, and cortical superficial siderosis. MRI can also show cortical edema and lesions with pathological enhancement in inflammatory forms of CAA.
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PET with amyloid-specific tracers to highlight amyloid deposition.
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Cerebrospinal fluid (CSF) analysis can be useful in the differential diagnosis with other pathologies.
Available therapies
There is no specific disease-modifying therapy for CAA. Treatment focuses on preventing hemorrhages and managing symptoms, including blood pressure control, and the management of seizures or cerebral edema. In diagnosed cases of CAA, it is crucial to avoid the use of anticoagulants and antiplatelet agents, particularly after a lobar hemorrhage, unless these medications are essential for the patient. In cases of inflammatory CAA (CAA-ri), corticosteroid therapy and sometimes immunosuppressive drugs are used.
Research in progress
Cerebral Amyloid Angiopathy (CAA) remains an underdiagnosed condition of great clinical significance, particularly due to the risk of hemorrhage and its link to dementia.
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Development of CSF and imaging biomarkers for early diagnosis.
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Genetic studies to better understand familial forms of the disease.
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Exploration of the role of neuroinflammation in disease progression.
Reference laboratory
Contacts and informations
Segreteria: Marco Milianti
Mail: segreteria.neurodeg@policlinico.mi.it 0255038508
Link a pubblicazioni scientifiche o risorse utili:
Centro per disturbi cognitivi e demenze (CDCD)