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. 2024 Apr;46(2):1527-1542.
doi: 10.1007/s11357-023-00883-6. Epub 2023 Aug 31.

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

Olivier Bousiges  1   2 , Benjamin Cretin  3   4 , Candice Muller  4 , Anne Botzung  3   4 , Lea Sanna  4 , Pierre Anthony  5   6 , Nathalie Philippi  3   5 , Catherine Demuynck  4 , Frédéric Blanc  3   4
Affiliations

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

Olivier Bousiges et al. Geroscience. 2024 Apr.

Abstract

ApoE4 as a risk factor for dementia with Lewy bodies (DLB) is still an issue. We sought to determine the involvement of ApoE4 according to different clinical parameters in our cohort of patients from Strasbourg, France. ApoE genotyping was performed on the AlphaLewyMA cohort. In this cohort, 197 patients were genotyped: 105 DLB patients, 37 Alzheimer's disease (AD) patients, 29 patients with AD/DLB comorbidity, and 26 control subjects (CS). The groups of patients were also classified according to the stage of evolution of the disease: prodromal or demented. We analyzed other parameters in relation to ApoE4 status, such as years of education (YOE) and Alzheimer CSF biomarkers. We observed a higher proportion of 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). We found a correlation between age at disease onset and YOE in the AD group (p = 0.039) but not in the DLB group (p = 0.056). Interestingly, in the DLB group, the subgroup of patients with high YOE (≥ 11) had significantly more patients with ApoE4 than the subgroup with low YOE (< 11). AD biomarkers did not seem to be impacted by the presence of ApoE4, except for Aβ42: DLB ApoE4-positive demented patients showed a more marked Aβ42 decrease. ApoE4 does not appear to be a risk factor for "pure" DLB patients. These results suggest a strong link between ApoE4 and amyloidopathy and consequently with AD. Trial registration: AlphaLewyMa, Identifier: NCT01876459, date of registration: June 12, 2013.

Keywords: Alzheimer’s disease; ApoE4; Cerebrospinal fluid biomarkers; Dementia; Dementia with Lewy bodies; Prodromal; Years of education.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of patient selection from the AlphaLewyMA cohort. AD Alzheimer’s disease, DLB dementia with Lewy bodies, LP lumbar puncture, Pro-AD prodromal-AD, Pro-DLB prodromal-DLB, AD-d AD-demented, DLB-d DLB-demented
Fig. 2
Fig. 2
Correlation between years of education and age at onset for pure DLB, pure AD, and AD/DLB. Years of education was correlated with age at onset for AD patients only (r = 0.4247, p = 0.039), although for DLB patients, the trend was strong (r = 0.2203, p = 0.056), whereas for the AD/DLB group, no correlation was observed (r =  − 0.02693, p = 0.918). Black dots represent non-ApoE4-carrier patients; red dots represent ApoE4-carrier patients. DLB dementia with Lewy bodies, AD Alzheimer’s disease, AD/DLB dementia with Lewy bodies and Alzheimer’s disease
Fig. 3
Fig. 3
Age at onset of disease as a function of ApoE4. Green labeling, DLB patients; black labeling, AD patients; red labeling, AD/DLB patients. DLB dementia with Lewy bodies, AD Alzheimer’s disease, AD/DLB dementia with Lewy bodies and Alzheimer’s disease
Fig. 4
Fig. 4
Biomarker levels according to ApoE4 presence. a DLB. b AD. c AD/DLB
Fig. 5
Fig. 5
Difference in Aβ42 levels between prodromal DLB and demented DLB for ApoE4 carriers and non-carriers
See this image and copyright information in PMC

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