Codeposition of cystatin C with amyloid-beta protein in the brain of Alzheimer disease patients

Immunohistochemical analysis of brains of patients with Alzheimer disease ( AD) revealed that the cysteine proteinase inhibitor cystatin C colocalizes with amyloid beta -protein (A beta) in parenchymal and vascular amyloid dep osits. No evidence of cerebral hemorrhage was observed in any of the brains studied. Immunoelectron microscopy demonstrated dual staining of amyloid f ibrils with anti-A beta and anti-cystatin C antibodies. Cystatin C immunore activity was also observed in amyloid deposits in the brain of transgenic m ice overexpressing human beta amyloid precursor protein. Massive deposition of the variant cystatin C in the cerebral vessels of patients with the Ice landic form of hereditary cerebral hemorrhage with amyloidosis is thought t o be responsible for the pathological processes leading to stroke. Anti-cys tatin C antibodies strongly labeled pyramidal neurons within cortical layer s most prone to amyloid deposition in the brains of AD patients. Immunohist ochemistry with antibodies against the carboxyl-terminus of A beta (x-42) s howed intracellular immunoreactivity in the same neuronal subpopulation. It remains to be established whether the association of cystatin C to A beta plays a primary role in amyloidogenesis of AD or is a late evens in which t he protein is bound to the previously formed A beta amyloid fibrils.