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Codistribution of Amyloid β Plaques and Spongiform Degeneration in Familial Creutzfeldt-Jakob Disease With the E200K-129M Haplotype
Nupur Ghoshal, MD, PhD;
Ignazio Cali, MS;
Richard Justin Perrin, MD, PhD;
S. Andrew Josephson, MD;
Ning Sun, MD, PhD;
Pierluigi Gambetti, MD;
John Carl Morris, MD
Arch Neurol. 2009;66(10):1240-1246.
Background Dominantly inherited Creutzfeldt-Jakob disease (CJD) represents 5% to 15% of all CJD cases. The E200K mutation in the prion protein (PrP) gene (PRNP) is the most frequent cause of familial CJD. Coexistent amyloid β (Aβ) plaques have been reported in some transmissible spongiform encephalopathies but to date have not been reported in familial CJD with the E200K mutation.
Objective To characterize a family with CJD in which Aβ plaques codistribute with spongiform degeneration.
Design Clinicopathologic and molecular study of a family with CJD with the E200K-129M haplotype.
Setting Alzheimer disease research center.
Participants Two generations of a family.
Main Outcome Measures Clinical, biochemical, and neuropathologic observations in 2 generations of a family.
Results In this kindred, 3 autopsied cases showed pathologic changes typical for the E200K-129M haplotype, including spongiform degeneration, gliosis, neuronal loss, and PrP deposition. Moreover, 2 of these cases (ages 57 and 63 years) showed numerous Aβ plaques codistributed with spongiform degeneration. APOE genotyping in 2 cases revealed that Aβ plaques were present in the APOE  4 carrier but not in the APOE 4 noncarrier. Two additional cases exhibited incomplete penetrance, as they had no clinical evidence of CJD at death after age 80 years but had affected siblings and children.
Conclusions To our knowledge, this is the first description of Aβ plaques in familial CJD with the E200K mutation. The codistribution of plaques and CJD-associated changes suggests that PrP plays a central role in Aβ formation and that Aβ pathology and prion disease likely in fluence each other. The kindred described herein provides support that PrPE200K may result in increased Aβ deposition.
Author Affiliations: Department of Neurology and Alzheimer's Disease Research Center (Drs Ghoshal, Perrin, and Morris) and Division of Neuropathology, Department of Pathology and Immunology (Drs Perrin and Morris), Washington University School of Medicine, St Louis, Missouri; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio (Mr Cali and Dr Gambetti); Department of Neurology, University of California, San Francisco (Dr Josephson); and DuPage Neurological Associates, Willowbrook, Illinois (Dr Sun).
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