Cerebral amyloid angiopathy: emerging concepts

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid deposition, primarily amyloid β-protein (Aβ) in older adults and Alzheimer's disease (AD) patients.
• CAA-associated vasculopathies contribute to hemorrhagic and ischemic brain lesions, as well as encephalopathies, linking CAA to dementia, stroke, and inflammation.
• Recent diagnostic advancements allow clinical CAA diagnosis without brain biopsies.

Purpose of the Study:

• To provide a comprehensive review of Cerebral Amyloid Angiopathy (CAA) and its related disorders.
• To cover epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis, treatment, and risk factors of CAA.
• To highlight recent advances in CAA diagnosis and its relationship with AD and other neurological conditions.

Main Methods:

• Review of current literature on Cerebral Amyloid Angiopathy (CAA).
• Analysis of diagnostic advancements including neuroimaging (MRI, PET) and cerebrospinal fluid (CSF) biomarkers.
• Discussion of the pathophysiology linking CAA to various neurological conditions and treatment strategies.

Main Results:

• Sensitive MRI techniques (T2(*) imaging, SWI) detect microhemorrhages and cortical superficial siderosis (cSS).
• Amyloid PET ligands can detect CAA but cannot differentiate vascular from parenchymal amyloid.
• CSF markers like Aβ40 and anti-Aβ antibodies show utility for CAA and CAA-related inflammation.
• Cortical superficial siderosis (cSS) is linked to transient focal neurological episodes (TFNE).
• CAA-related inflammation shares mechanisms with amyloid-related imaging abnormalities (ARIA) in AD immunotherapy.

Conclusions:

• CAA is a significant factor in dementia, stroke, and encephalopathies, with increasing diagnostic capabilities.
• Neuroimaging and fluid biomarkers are crucial for non-invasive CAA diagnosis and management.
• Understanding CAA pathophysiology is key to developing effective treatments and managing related inflammatory conditions.