The histological features of
familial cerebral amyloid angiopathy (British type) with non-neuritic
amyloid plaque formation (FAB) include deposition of
amyloid, (supposedly associated with the C-terminal fragments of both alpha- and
beta-tubulin), in small cerebral and spinal arteries, hippocampal
amyloid plaques and neurofibrillary tangles (NFTs) as well as ischaemic white matter changes. In the present study we report on the cytoskeletal pathology that occurs in association with FAB. Sections from the hippocampus and cerebellum of three cases from three unrelated families were stained with
silver impregnation methods and
antibodies to
antigens including tau, neurofilaments,
ubiquitin and
glial fibrillary acidic protein. Electron microscopic examination of the hippocampus was carried out in one case. All hippocampal subregions contained large numbers of NFTs and neuropil threads (NT), which were stained with both phosphorylation-dependent and phosphorylation-independent tau
antibodies and ultrastructurally were found to be composed of paired helical filaments (PHFs). Although the majority of the
amyloid plaques were of the non-neuritic type, distended PHF-containing and tau-positive neurites were seen in close proximity of a minority of the hippocampal plaques. The perivascular
amyloid deposits of the cerebellum contained numerous
ubiquitin-positive granular elements similar to those seen in cerebellar A
beta amyloid plaques in
Alzheimer's disease. In FAB severe cytoskeletal pathology is present in areas most affected by
amyloid plaque deposits, thus suggesting a localised neurotoxic effect of the poorly characterised amyloidogenic
peptide characteristic of this condition.