GIANT-CELL ARTERITIS IN ASSOCIATION WITH CEREBRAL AMYLOID ANGIOPATHY - IMMUNOHISTOCHEMICAL AND MOLECULAR STUDIES (VOL 28, PG 1237, 1997)

Giant Cell arteritis (GCA) usually manifests as a transmural vascular infiltrate of mononuclear and multinucleated giant cells (MNGC). We de scribe six patients with GCA associated with severe cerebral amyloid a ngiopathy (CAA), all with cerebral hemorrhage or varying degrees of ce rebral infarct, and histological evidence of Alzheimer's disease (cort ical CAA often predominating over senile plaques and neurofibrillary t angles). One case showed mostly cortical involvement (with old microhe morrhages), and the others were primarily leptomeningeal (with involve ment of the underlying cortex and extensive encephalomalacia of adjace nt brain). Many vessels with CAA exhibited a pronounced adventitial an d perivascular infiltrate of lymphocytes, histiocytes, and MNGC. Immun ohistochemical staining showed deposition of beta/A4 peptide primarily in the thickened media of CAA vessels, and within the cytoplasm of MN GC-suggesting phagocytosis of insoluble peptide. Cystatin C antibody s tained vascular amyloid and diffusely highlighted astrocytic and MNGC cytoplasm. HAM56-positive macrophages were frequently seen around amyl oid-laden vessels. Anti-smooth muscle actin immunohistochemistry sugge sts the occurrence of medial destruction by amyloid, with relative pre servation of intimal cells. Ultrastructural studies performed in one c ase confirmed the presence of intracytoplasmic amyloid in MNGC. The GC A seen in these cases of CAA most likely represents a foreign body res ponse to amyloid proteins, causing secondary destruction of the vessel walt. DNA from brain tissues of five affected patients was examined t o assess whether mutations were present in exon 17 of the APP gene or exon 2 of the cystatin C gene, a finding that might explain the foreig n body giant cell response to amyloid proteins in these cases. However , restriction fragment mapping of amplified gene segments showed that previously described mutations were not present in these cases. Copyri ght (C) 1998 by W.B. Saunders Company.