Objective: To investigate the association between Apolipoprotein E (APOE) genotype and freezing of gait (FOG) in Parkinson’s disease (PD).

Background: This cohort study using the PPMI data included 339 early PD patients who were divided into APOE ε4-positive (n=88) and ε4-negative (n=251) groups. They were followed-up over up to 6 years to identify the development of FOG. To investigate the influence of CSF β‐amyloid 1-42 (Aβ₄₂) on their association, the patients were additionally dichotomized into “high-level” and “low-level” groups according to CSF Aβ₄₂ levels (cutoff=258 pg/ml).

Method: This cohort study using the PPMI data included 339 early PD patients who were divided into APOE ε4-positive (n=88) and ε4-negative (n=251) groups. They were followed-up over up to 6 years to identify the development of FOG. To investigate the influence of CSF β‐amyloid 1-42 (Aβ₄₂) on their association, the patients were additionally dichotomized into “high-level” and “low-level” groups according to CSF Aβ₄₂ levels (cutoff=258 pg/ml).

Results: At baseline, the APOE ε4-positive group had lower CSF Aβ₄₂ levels than the APOE ε4-negative group. During a median follow-up of 5.0 years, the APOE ε4-positive group had a higher incidence of FOG than the APOE ε4-negative group. In the multivariable Cox model excluding CSF Aβ₄₂, APOE ε4 was a significant predictor of FOG. However, after adding CSF Aβ₄₂ in the model, APOE ε4 did not survive, whereas lower CSF Aβ₄₂ levels were associated with FOG. In subgroup analyses according to CSF Aβ₄₂ levels, the effect of APOE ε4 allele was not found in the “low-level” group. However, in the “high-level” group, the APOE ε4 allele independently increased the risk of FOG, and this association was stronger than the association with CSF Aβ₄₂.

Conclusion: We found the APOE ε4 allele as a novel genetic risk factor for FOG in early PD. This association seemed to be mainly mediated by Aβ-dependent pathways, but its Aβ-independent effects might also contribute to the development of FOG.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/apolipoprotein-e-%ce%b54-and-risk-of-freezing-of-gait-in-early-parkinsons-disease/