AUTOSOMAL-DOMINANT ARTERIOPATHIC LEUKO-ENCEPHALOPATHY AND ALZHEIMERS-DISEASE

A 49-year-old man suffered from progressive dementia and seizures lead ing to death after 2 years. CT scans showed severe cortical-subcortica l atrophy and hypodensity of the white matter. His father had died at about the same age with similar clinical signs. Two sisters and one br other were also affected. Neuropathological study revealed predominant involvement of the cerebral white matter with myelin loss, gliosis an d type I lacunes. The small arteries and arterioles of the white matte r and basal ganglia, and, to a lesser extent those of the subarachnoid al space, displayed fibrosis and replacement of the media by an eosino philic, PAS positive, Congo Red negative, granular substance. Electron microscopy showed swollen myocytes surrounded by collagen, elastin an d a compact electron-dense material. Immunofluorescence using antibodi es against IgA, IgG, IgM, Clq and C3 stained the abnormal media weakly . In the cortex, there were diffuse senile plaques and neurofibrillary tangles. Immunohistochemistry demonstrated beta/A4 positive material in cortical senile plaques but not in arterial walls. Adventitial macr ophages were, however, immunoreactive for gamma-trace. Systemic arteri oles were normal. The vascular changes and leukoencephalopathy are com parable to those described in 'Cerebral Autosomal Dominant Arteriopath y with Subcortical Infarcts and Leukoencephalopathy' (CADASIL). Simila r vascular changes were also observed in nonfamilial cases. An associa tion with Alzheimer changes in the cortex has not been described previ ously. The relationship between both diseases and the role of each in the causation of the dementia is unclear.