Amyloid-β 1-42 Levels are Modified by Apolipoprotein E ε4 in Creutzfeldt-Jakob Disease in a Similar Manner as in Alzheimer's Disease

The presence of apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and associated with a more pronounced reduction of amyloid-beta 1-42 (A beta(1-42)) in the cerebrospinal fluid (CSF). Because a decrease of A beta(1-42) 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 epsilon 4 in sporadic CJD (sCJD), in particular the influence on the CSF-markers 14-3-3 protein, tau protein, neuron-specific enolase, S100 protein, A beta(1-42), and A beta(1-40). No differences in the ApoE epsilon 4 allele frequency and ApoE genotype distribution between sCJD and published healthy controls were observed. The ApoE epsilon 4 allele had no effect on disease duration or age at onset. We detected a dose-dependent ApoE epsilon 4 effect on the decrease of A beta(1-42) in sCJD. ApoE epsilon 4 carriers with one ApoE epsilon 4 allele showed significantly reduced A beta(1-42) values (p < 0.0001) in comparison with non-carriers. ApoE epsilon 4 allele is not a risk factor for sCJD but modifies the A beta(1-42) levels in CSF in a similar manner as in AD. Based on our results in sCJD patients, we hypothesize that the ApoE epsilon 4 effect on A beta(1-42) values might not be disease-specific.