Cerebral amyloid angiopathy with co-localization of prion protein and beta-amyloid in an 85-year-old patient with sporadic Creutzfeldt-Jakob disease

Abstract

We report on an 85-year-old woman with hypertensive cerebral arteriolosclerosis who presented with rapidly progressive encephalopathy leading to death within 4 months. Magnetic resonance imaging showed mild cortical atrophy consistent with her age and diffuse leukoaraiosis. Her CSF 14-3-3 protein was positive. Neuropathology showed severe spongiform change and gliosis in the grey matter and immunohistochemistry revealed diffuse prion protein deposition in a predominant synaptic pattern. She had no family history of neurological disorder and genotyping did not show any prion protein gene mutation, in keeping with a diagnosis of sporadic Creutzfeldt-Jakob disease. There was also diffuse amyloid angiopathy involving the cortical and leptomeningeal arterioles of the cerebral hemispheres and cerebellum and the capillaries of the grey matter. The amyloid angiopathy expressed beta-amyloid but also prion protein and double immunostaining confirmed co-localization of both proteins in many vessel walls. Alzheimer's type pathology was restricted to a few diffuse beta-amyloid plaques in the entorhinal cortex and rare tangles in the hippocampus. Deposition of prion protein in cerebral vessels has been reported in a single case of stop codon 145 mutation of the PRNP gene. Co-localization of beta-amyloid and prion protein in the same amyloid plaque has been described in elderly patients with Creutzfeldt-Jakob or Gerstmann-Sträussler-Scheinker diseases but only exceptionally in cerebral amyloid angiopathy. In this patient, hypertensive cerebrovascular disease may have contributed to the failure to eliminate both proteins from the brain.