Solubilized cystatin C amyloid is cytotoxic to cultured human cerebrovascular smooth muscle cells.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid within arteries of the cerebral cortex and leptomeninges. This condition is age related, especially prevalent in Alzheimer's disease (AD) and the main feature of certain hereditary disorders. The vascular smooth muscle cells (VSMC) appear to play a vital role in the development of CAA and have been found to produce the amyloid beta precursor protein (AbetaPP) and process it to Abeta the major component of most CAA amyloid. Moreover, synthesized Abeta has proven to be toxic to cerebral VSMC in culture possibly explaining the disintegration and disappearance of the muscle cells from affected cerebral blood vessels seen in CAA. An aggressive and extremely rare form of CAA, known as Hereditary Cerebral Hemorrhage With Amyloidosis-Icelandic Type (HCHWA-I), exhibits this withdrawal of VSMC as amyloid accumulates in the vessel wall. However, the amyloid in HCHWA-I is made from a variant of cystatin C (L68Q) instead of the more common Abeta. To evaluate possible cytotoxicity in this condition solubilized cystatin C amyloid extracted from HCHWA-I leptomeninges was applied to cerebral smooth muscle cells in culture and was found to kill the cells.