Localization of blood proteins thrombospondin1 and ADAMTS13 to cerebral corpora amylacea

Abstract

Corpora amylacea (CA) have long been described in aging brains and in patients with neurodegenerative conditions, but their origins have been debated. It has been proposed that CA represent collections of nervous system breakdown products that accumulate within astrocytic cytoplasm. In support of this, studies have shown that CA include glycosylated material, ubiquitin, and an assortment of proteins derived from neuronal cytoplasm. On the other hand, many of these proteins are not specifically localized to neurons or astrocytes; some components of CA, such as complement proteins, are most abundantly expressed outside the central nervous system. The characteristic predilection for CA to accumulate near vessels and ependyma suggests that proteins extravasated from blood or transudated from CSF may form a component of these structures. In this study, we report the immunohistochemical localization of blood and platelet proteins thrombospondin1 and ADAMTS13 in CA from aged individuals and patients with vascular dementia. Thrombospondin1 localized to neurons, but was most prominently localized to CA. An independent serum and platelet expressed protein, ADAMTS13, was found in CA in the same brain regions. In vitro analysis shows that thrombospondin1 and ADAMTS13 form complexes together in cells and in direct protein binding assays. We speculate that CA could result from a conglomeration of interacting proteins from degenerating neurons and from extravasated blood elements released after transient breakdown of the blood-brain barrier.