Affiliations: [a] National Reference Center for TSE Surveillance at Department of Neurology, University Medical School, Göttingen, Germany | [b] Department of Medical Statistics, University Medical School, Göttingen, Germany | [c] Department of Clinical Chemistry, University Medical School, Göttingen, Germany
Correspondence:
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Correspondence to: Daniela Varges, MD, National Reference Center for TSE Surveillance, Department of Neurology, University Medical School, Robert-Koch Str. 40, D-37075 Göttingen, Germany. Tel.: +49 551 396636; Fax: +49 551 397020; E-mail: [email protected].
Note: [+] Deceased.
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.
Keywords: Alzheimer's disease, amyloid-β, apolipoprotein E, codon 129 genotype, Creutzfeldt-Jakob disease, dementia, prion, tau
