Codistribution of amyloid beta plaques and spongiform degeneration in familial Creutzfeldt-Jakob disease with the E200K-129M haplotype.
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 beta (Abeta) 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 Abeta plaques codistribute with spongiform degeneration.


METHODS
Clinicopathologic and molecular study of a family with CJD with the E200K-129M haplotype.


METHODS
Alzheimer disease research center.


METHODS
Two generations of a family.


METHODS
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 Abeta plaques codistributed with spongiform degeneration. APOE genotyping in 2 cases revealed that Abeta plaques were present in the APOE epsilon4 carrier but not in the APOE epsilon4 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 Abeta plaques in familial CJD with the E200K mutation. The codistribution of plaques and CJD-associated changes suggests that PrP plays a central role in Abeta formation and that Abeta pathology and prion disease likely in fluence each other. The kindred described herein provides support that PrP(E200K) may result in increased Abeta deposition.
Ghoshal
Nupur
N
Department of Neurology and Alzheimer's Disease Research Center, Washington University School of Medicine, 4488 Forest Park Ave, Ste 101, St Louis, MO 63108, USA. ghoshaln@neuro.wustl.edu
Cali
Ignazio
I
Perrin
Richard Justin
RJ
Josephson
S Andrew
SA
Sun
Ning
N
Gambetti
Pierluigi
P
Morris
John Carl
JC
D017668:Age of Onset; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000473:pathology*; D019286:Endopeptidase K / Q000737:chemistry; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology*; D010375:Pedigree; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics
D001057:Apolipoproteins E; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D019286:Endopeptidase K