Cytoskeletal pathology in familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation

The histological features of familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation (FAB) include deposition o f amyloid, (supposedly associated with the C-terminal fragments of both alp ha- and beta-tubulin). in small cerebral and spinal arteries, hippocampal a myloid plaques and neurofibrillary tangles (NFTs) as well as ischaemic whit e matter changes. In the present study we report on the cytoskeletal pathol ogy that occurs in association with FAB. Sections from the hippocampus and cerebellum of three cases from three unrelated families were stained with s ilver impregnation methods and antibodies to antigens including tau, neurof ilaments, ubiquitin and glial fibrillary acidic protein. Electron microscop ic examination of the hippocampus was carried out in one case. All hippocam pal subregions contained large numbers of NFTs and neuropil threads (NT), w hich were stained with both phosphorylation-dependent and phosphorylation-i ndependent tau antibodies and ultrastructurally were found to be composed o f paired helical filaments (PHFs). Although the majority of the amyloid pla ques were of the non-neuritic type, distended PHF-containing and tau-positi ve neurites were seen in close proximity of a minority of the hippocampal p laques. The perivascular amyloid deposits of the cerebellum contained numer ous ubiquitin-positive granular elements similar to those seen in cerebella r A beta amyloid plaques in Alzheimer's disease. In FAB severe cytoskeletal pathology is present in areas most affected by amyloid plaque deposits, th us suggesting a localised neurotoxic effect of the poorly characterised amy loidogenic peptide characteristic of this condition.