Cerebral amyloid angiopathy

Abstract

Sporadic cerebral amyloid angiopathy (CAA) is cerebral small vessel disease characterized by deposition of amyloid β (Aβ) in the walls of small arteries and capillaries in the cerebral cortex and leptomeninges. CAA is the most important cause of lobar intracerebral hemorrhage (ICH) in the elderly. It is also frequently detected in patients with Alzheimer disease (AD). Disturbance of intramural periarterial drainage (IPAD) and glymphatic system are thought to contribute to the development and progression of CAA. In particular, the localization of Aβ deposition is consistent with the IPAD pathway, suggesting that disruption of IPAD is directly involved in the development of CAA.

Recent advances in magnetic resonance imaging (MRI) have made it possible to detect CAA–related brain lesions noninvasively. These CAA–related MRI markers include lobar cerebral microbleed (CMB), convexity subarachnoid hemorrhage (cSAH)/cortical superficial siderosis (cSS), enlarged perivascular space in the centrum semiovale, white matter hyperintensity in posterior predominance or multiple subcortical spot pattern, and cortical microinfarcts. Currently, the modified Boston criteria is widely used, which includes lobar, cortical or cortical–subcortical hemorrhage (ICH, CMB) and cSS as CAA–related hemorrhagic marker.

The clinical aspects of CAA include symptomatic lobar ICH, cognitive dysfunction, transient focal neurological episodes (TFNE), and CAA–related inflammation (CAA–ri). CAA–related lobar ICH is more common in women, increases with age, and is characterized by a high recurrence rate. cSS / cSAH is attracting attention as a risk of CAA–related ICH. CAA affects cognitive function independently of AD pathology. It has been suggested that cognitive dysfunction is related to the neurodegeneration associated with CAA caused by chronic cerebral hypoperfusion, decreased vascular reactivity, microbleeds, microinfarcts, and white matter lesions. TFNE is a transient focal neurological symptom associated with CAA, including paresthesia, limb weakness and aphasia. Cortical spreading deporalization triggered by cSAH/cSS is considered to be the pathogenic mechanisms. CAA–ri is an acute to subacute clinical form that presents headache, disturbance of consciousness, cognitive dysfunction or seizures with asymmetric white matter lesions reflecting vasogenic edema on brain MRI. The transient appearance of anti–Aβ antibodies in the cerebrospinal fluid suggests an autoimmune mechanism, and immunotheraphy can be effectively. Similarities with amyloid–related imaging abnormalities (ARIA) in immunotherapy for AD have also been noted.

There is no effective treatment for CAA at this time. A phase II trial of ponezumab, an Aβ40–selective monoclonal antibody, was conducted as a disease–modifying therapy, but showed no efficacy. Animal studies have shown the efficacy of some drugs such as cilostazol, dabigatran, taxifolin, memantine, metformin as potential therapeutic agents. Anti–ApoE antibody, which selectively binds to human apolipoprotein E, is also expected as drug candidates.