Biomarkers of Cerebral Amyloid Angiopathy and Neuropathological Relationship with Alzheimer's Disease

Cerebral amyloid angiopathy (CAA), characterized by beta-amyloid (Aβ) deposits within small- to medium-sized blood vessels of the brain and leptomeninges, is known to be associated with an elevated risk of lobar intracerebral hemorrhage. Clinical diagnosis of CAA is complicated due to the limited diagnosis methods and lack of biomarkers for this disease. It was found that CAA has a significantly high probability of comorbidity with Alzheimer's disease (AD) due to the similar neuropathological characteristics known as amyloid-related imaging abnormalities (ARIA). Anti-Aβ monoclonal antibody therapy has been extensively investigated in the treatment of AD patients and applied in several clinical trials worldwide. However, common side effects such as hemorrhage and edema may occur for patients with preclinical or asymptomatic CAA when using antibody therapy. Therefore, it is crucial to identify CAA comorbidity in AD patients before starting anti-Aβ monoclonal antibody therapy. This review summarizes the clinical diagnostic methods and related biomarkers for AD and CAA. Further investigation of CAA for its neuropathological relationship with AD and the discovery of novel biomarkers may pave the way for a more accurate diagnosis and effective prevention of harmful side effects during treatment. It is of great importance to avoid adverse outcomes such as cerebral hemorrhage and edema caused by CAA in the treatment of AD and CAA comorbid patients.