Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): II--A review of histopathological aspects.

Cerebral amyloid-beta (A beta) angiopathy is the histopathological hallmark of hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D). A beta deposits are found mainly in the cerebral and cerebellar meningocortical blood vessels and as plaques throughout the cerebrocortical gray matter. A beta deposition in arteries and arterioles starts at the junction of media and adventitia and proceeds to involve the media causing degeneration of the vascular smooth muscle cells. Cerebrocortical arterioles often show one or two layers of radial A beta around a layer of homogenous A beta that replaces the media. Degenerating neurites, reactive astrocytes and microglial cells may surround cerebrocortical angiopathic arterioles and capillaries, probably in reaction to invasion of the perivascular neuropil by A beta fibrils. Furthermore, clusters of coarse extracellular matrix deposits may be found near A beta-laden cerebrocortical arterioles. The amyloid-associated proteins, cystatin C, and beta PP colocalize diffusely with Dutch vascular A beta, whereas HLA-DR immunoreactivity is found only in the periphery of the diseased vessel wall. The latter phenomenon may be related to the presence of perivascular cells. Angiopathic blood vessels frequently show structural changes. The relation of the described pathology to the development of hemorrhage, infarction and leukoencephalopathy needs further elucidation.