Amyloid-β 1-42 levels are modified by apolipoprotein E ε4 in Creutzfeldt-Jakob disease in a similar manner as in Alzheimer's disease.

Abstract

The presence of apolipoprotein E (ApoE) ε4 allele is a risk factor for Alzheimer's disease (AD) and associated with a more pronounced reduction of amyloid-β 1-42 (Aβ1-42) in the cerebrospinal fluid (CSF). Because a decrease of Aβ1-42 and increase of tau protein levels, both important biomarkers for AD, are also reported in Creutzfeldt-Jakob disease (CJD), we analyzed if a similar relationship can be observed in this rapid progressive dementia. Our study included 309 patients with sporadic CJD (147 neuropathologically confirmed and 162 probable cases). We analyzed the role of ApoE ε4 in sporadic CJD (sCJD), in particular the influence on the CSF-markers 14-3-3 protein, tau protein, neuron-specific enolase, S100 protein, Aβ1-42, and Aβ1-40. No differences in the ApoE ε4 allele frequency and ApoE genotype distribution between sCJD and published healthy controls were observed. The ApoE ε4 allele had no effect on disease duration or age at onset. We detected a dose-dependent ApoE ε4 effect on the decrease of Aβ1-42 in sCJD. ApoE ε4 carriers with one ApoE ε4 allele showed significantly reduced Aβ1-42 values (p < 0.0001) in comparison with non-carriers. ApoE ε4 allele is not a risk factor for sCJD but modifies the Aβ1-42 levels in CSF in a similar manner as in AD. Based on our results in sCJD patients, we hypothesize that the ApoE ε4 effect on Aβ1-42 values might not be disease-specific.

• Authors: Daniela Varges, Klaus Jung, Joanna Gawinecka, Uta Heinemann, Matthias Schmitz, Nicolas von Ahsen, Anna Krasnianski, Victor W Armstrong, Inga Zerr
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 23 Issue 4 Pg. 717-26 ( 2011) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 21157024 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Apolipoprotein E4
• Biomarkers
• Peptide Fragments
• amyloid beta-protein (1-42)

Topics

• Adult
• Aged
• Aged, 80 and over
• Alzheimer Disease (cerebrospinal fluid, diagnosis, genetics)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Apolipoprotein E4 (genetics)
• Biomarkers (cerebrospinal fluid)
• Creutzfeldt-Jakob Syndrome (cerebrospinal fluid, diagnosis, genetics)
• Female
• Gene Frequency (genetics)
• Humans
• Male
• Middle Aged
• Peptide Fragments (cerebrospinal fluid)