Involvement of ApoE4 in dementia with Lewy bodies in the prodromal and demented stages: evaluation of the Strasbourg cohort

Abstract Background: ApoE4 as a risk factor for AD is no longer a matter of debate. However, it is still an issue for dementia with Lewy bodies (DLB). We wanted to determine the involvement of ApoE4 according to different clinical parameters in our cohort of patients from Strasbourg. Methods: ApoE genotyping was performed on the AlphaLewyMA cohort. In this cohort, 197 patients were genotyped. Among them 105 DLB patients, 37 Alzheimer’s disease (AD), 29 comorbidity AD/DLB and 26 control subjects (CS). These groups are also classified according to the stage of evolution of the disease: prodromal or demented. We analyzed other parameters in relation to ApoE4, such as socio-educational levels (SEL) and Alzheimer CSF biomarkers (t-Tau, P-Tau, Aβ-42 and Aβ40). Results: There were significantly more ApoE4 carriers in the AD (51.4%) and AD/DLB (72.4%) groups compared to the DLB (25.7%) and CS (11.5%) groups (P<0.0001). No significant difference was found between the percentage of ApoE4 in the DLB and CS groups, idem between AD and AD/DLB groups. For AD group, we find a correlation between the age of onset of the disease and the SEL. For DLB group, the correlation does not reach significance despite a strong trend (p = 0.056). Interestingly, in this latter group, taking the median of SEL (Education=11 years, i.e. one year before bachelor), the group of patients with high SEL (≥ 11) has significantly more patients with ApoE4 than the group of patients with low SEL (<11). Finally, the AD biomarkers do not seem to be impacted by the presence of ApoE4, except for Aβ42. DLB ApoE4 demented patients show a more marked decrease of CSF Aβ42. Conclusions: ApoE4 does not appear to be a risk factor for “pure” DLB patients with the possible exception of patients with high SEL. In the DLB group, ApoE4 would be responsible for the Aβ42 decrease between the prodromal and demented group, suggesting a strong link between ApoE4 and amyloidopathy thus confirming its strong link with AD. Trial registration : ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)