Cerebral amyloid angiopathy without and with cerebral hemorrhages: A comparative histological study

Abstract

To identify those factors associated with cerebral hemorrhage among brains with cerebral amyloid angiopathy (CAA), we undertook a comparative postmortem histopathological study of amyloid-containing vessels in the brains of patients with and without hemorrhage. Those without hemorrhage were represented by the following two groups: (1) elderly patients from a large general hospital (n = 66; age range, 75-107 years) and (2) patients with various neuropsychiatric disorders (n = 70; age range, 27-96 years). CAA was found in 45% of the first group and in 54% of the second group. The findings in these patients were compared with those in 17 brains in which both CAA and cerebral hemorrhage were present. We found that CAA was more severe in the brains with cerebral hemorrhage than in those without, and that fibrinoid necrosis was seen only in the brains with cerebral hemorrhage (12 of the 17 brains). Microaneurysms occurred only in the presence of severe, rather than moderate or mild, CAA. Serial sections in 2 brains of patients with cerebral hemorrhage showed fibrinoid necrosis, microaneurysms, and vascular rupture in close association with the hemorrhage. In 2 patients, hemorrhage was precipitated by trauma, and in 1, it was secondary to metastatic carcinoma. The features of brains from patients with CAA that are most consistently related to cerebral hemorrhage are (1) a severe degree of CAA and (2) the presence of fibrinoid necrosis, with or without microaneurysms.

Ischemic brain injury in cerebral amyloid angiopathy

“…Cerebral amyloid angiopathy is characterized by the accumulation of A in the vessel wall of small cortical and leptomeningeal arteries and arterioles, and to a lesser extent in the wall of cortical capillaries. 15,16 The process of A accumulation in CAA is not fully understood. An earlier theory suggested that A in CAA directly originates from smooth muscle cells in the vessel wall.…”

“…Moderate CAA is often defined as circumferential staining of A in leptomeningeal and cortical blood vessels, while severe CAA is usually characterized by additional vascular pathologies such as concentric splitting of the vessel wall (double barreling) or appearance of A in the perivascular neuropil (dyshoric changes). 12,16,29 Moderate-to-severe CAA seems to be most strongly associated with clinical symptoms. 12 Cerebral amyloid angiopathy is not equally distributed throughout the brain, but predominantly affects vessels in posterior cortical brain regions, 8,30 whereas vessels in the brain stem and basal ganglia are relatively spared.…”

Human postmortem brain-derived cerebrovascular smooth muscle cells express all genes of the classical complement pathway: A potential mechanism for vascular damage in cerebral amyloid angiopathy and Alzheimer's disease

“…Cerebral amyloid angiopathy (CAA) is found in approximately 90% of AD cases and consists of deposits of amyloid beta (Aβ) peptide in and around the perivascular spaces of vessels (Premkumar et al, 1996). This eventually leads to the death of smooth muscle cells and endothelial cells in the vicinity of amyloid deposits (Vonsattel et al, 1991). The presence of Aβ deposits in the vasculature can also lead to proinflammatory responses including microglia/macrophage activation (Giulian et al, 1995) and complement activation (McGeer et al, 1989).…”

Treatment Targets in Intracerebral Hemorrhage

“…These amyloid deposits are similar to those seen in Alzheimer's disease. The amyloid-beta fragment is the primary component of the plaques [18,19].…”