Involvement of Dab1 in APP processing and beta-amyloid deposition in sporadic Creutzfeldt-Jakob patients.
Alzheimer's disease and prion pathologies (e.g., Creutzfeldt-Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of amyloid precursor protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in 17 cases of sporadic CJD (sCJD) post-mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrP(sc) types 1 and 2. One group with PrP(sc) type 1 showed increased Dab1 phosphorylation and lower betaCTF production with an absence of Abeta deposition. The second sCJD group, which carried PrP(sc) type 2, showed lower levels of Dab1 phosphorylation and betaCTF production, and Abeta deposition. Thus, the present observations suggest a correlation between Dab1 phosphorylation, Abeta deposition and PrP(sc) type in sCJD.
Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia and Department of Cell Biology, University of Barcelona, Baldiri Reixac 15-21, Barcelona, Spain.
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R
Gavín
I
I
Ferrer
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JA
del Río
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C115785:DAB1 protein, human; D009419:Nerve Tissue Proteins; D018620:PrPSc Proteins; D053829:Amyloid Precursor Protein Secretases