Association between deposition of beta-amyloid and pathological prion protein in sporadic Creutzfeldt-Jakob disease.
BACKGROUND
Alzheimer's disease (AD) and prion diseases such as sporadic Creutzfeldt-Jakob disease (sCJD) share common features concerning their molecular pathogenesis and neuropathological presentation and the coexistence of AD and CJD in patients suggest an association between the deposition of the proteolytically processed form of the amyloid precursor protein, beta-amyloid (Abeta), which deposits in AD, and the abnormal form of the prion protein, PrP(Sc), which deposits in sCJD.


METHODS
We have characterized sCJD patients (n = 14), AD patients (n = 5) and nondemented controls (n = 5) with respect to the deposition of PrP(Sc) and Abeta morphologically, biochemically and genetically and correlated these findings to clinical data.


RESULTS
sCJD-diseased individuals with abundant deposits of Abeta present with a specific clinicopathological profile, defined by higher age at disease onset, long disease duration, a genetic profile and only minimal amounts of PrP(Sc) in the cerebellum.


CONCLUSIONS
The co-occurrence of pathological changes typical for sCJD and AD in combination with the inverse association between accumulation of Abeta and PrP(Sc) in a subgroup of sCJD patients is indicative of common pathways involved in the generation or clearance of Abeta and PrP(Sc) in a subgroup of sCJD patients.
Debatin
Laura
L
Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
Streffer
Johannes
J
Geissen
Markus
M
Matschke
Jakob
J
Aguzzi
Adriano
A
Glatzel
Markus
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000235:genetics; D015153:Blotting, Western; D001923:Brain Chemistry; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D016133:Polymerase Chain Reaction; D018620:PrPSc Proteins / Q000032:analysis*; D053764:Presenilin-1 / Q000032:analysis / Q000235:genetics; D053766:Presenilin-2 / Q000032:analysis / Q000235:genetics; D000072002:Prion Proteins; D011328:Prions / Q000032:analysis / Q000235:genetics; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C512656:PRNP protein, human; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D018620:PrPSc Proteins; D053764:Presenilin-1; D053766:Presenilin-2; D000072002:Prion Proteins; D011328:Prions; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C075222:amyloid beta-protein (1-42)