THE NEUROPATHOLOGY OF WILLIAMS-SYNDROME - REPORT OF A 35-YEAR-OLD MAN WITH PRESENILE BETA/A4 AMYLOID PLAQUES AND NEUROFIBRILLARY TANGLES

Objective: To study neuropathologically Williams syndrome in a 35-year-old patient. Methods: Sections from multiple regions of the brain were examined with luxol fast blue and hematoxylineosin staining, and selected sections were stained with the silver impregnation technique (Bielschowsky technique) and Congo red. In addition, immunohistochemistry with monoclonal antibodies against glial fibrillary acidic protein, beta/A4 amyloid, paired helical filaments, and phosphorylated tau protein was performed on cortical, hippocampal, amygdaloid, and basal ganglian sections. Results: No specific macroscopic or microscopic abnormalities were recognized that are specific for Williams syndrome. The histopathologic examination did, however, demonstrate the presence of Alzheimer-type changes, including beta/A4 amyloid-containing senile plaques and scattered neurofibrillary tangles in neocortex and medial temporal lobe structures (entorhinal cortex, CA1 area of the hippocampus, and amygdala). Plaques were most numerous in the amygdala (7/mm(2)) and in the entorhinal cortex (4/mm(2)). Neurofibrillary tangles were less numerous (<1/mm(2)), except in the hippocampus, where approximately 2/mm(2) were found. Conclusions: To our knowledge, ours represents the first neuropathologic description of a patient with Williams syndrome. Although Williams syndrome is usually sporadic, familial cases have been reported along with candidate chromosomal loci. If our findings are confirmed in additional patients with Williams syndrome, they map provide clues to other factors that are important in the pathogenesis of senile plaques (with beta/A4 amyloid deposition) and neurofibrillary tangles.