Cerebral Amyloid Angiopathy Associated with Cerebral Hemorrhage with the Deposition of Cystatin C: Study on Japanese Cases

To characterize the cerebral amyloid angiopathy (CAA) in Japan causing cerebral hemorrhage (CH) and consequential vascular dementia (VD), we examined brains of CAA with CH by enzyme immunohistochemis-try and gene analysis. We also established enzyme-linked immunosorbent assay (ELISA) to estimate the levels of cystatin C (CC) in cerebrospinal fluid (CSF) from patients with CH comparing with reference cases. Some CAA patients had possible family history of CAA and the others were sporadic. Most of them were aged and normotensive. Amyloid of these Japanese type CAA showed the β-protein (BP) antigenicity coexisting with that of CC. Some of patients with CH showed a low concentration CC in CSF together with clinical manifestations of CAA. Brain tissues from two of them were examined immunohistochemically and amyloid of CAA showed antigenicity of CC and BP. Analysis of CC cDNA of Japanese case did not show the Alu I restriction fragment length polymorphism (RFLP) as recognized in the Icelandic HCHWA. The results suggest the presence of not only familial but also sporadic cases of CAA with the deposition of CC associated with CH, causing VD in the normotensive elderly. Abnormal metabolism or malfunction of CC as protease inhibitor may play some roles in CH of CAA. The ELISA method is simple to perform and appears to be useful tool for diagnosing patients with suspected CAA with CH and the deposition of CC.