Relapse-associated worsening in apolipoprotein E ε4 carriers with relapsing multiple sclerosis

Area of Science:

• Neurology
• Genetics
• Immunology

Background:

• Multiple sclerosis (MS) involves disability accrual from relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA).
• Genetic factors influence MS severity, but the role of the apolipoprotein E (ApoE) gene in disability accrual remains unclear.
• The apolipoprotein E ε4 allele (ApoE4) is a significant genetic factor in various neurological conditions.

Purpose of the Study:

• To investigate the impact of the ApoE ε4 allele (ApoE4) on disability accrual patterns in relapsing-remitting multiple sclerosis (RRMS) patients.
• To determine if ApoE4 influences the likelihood of developing PIRA versus RAW.
• To explore the association between ApoE4 carriage and the rate of confirmed disability accrual (CDA) in MS.

Main Methods:

• Recruited 160 relapsing MS patients (aged >18) from the University of Florence MS center.
• Classified patients into ApoE4 carriers and non-carriers.
• Utilized multivariable Cox proportional hazard regressions to assess the association between ApoE4 and the type of first CDA, defining PIRA and RAW based on relapse timing relative to disability events.

Main Results:

• A first CDA occurred in 97 patients (60.6%) over a mean follow-up of 12.3 years.
• PIRA accounted for 59.8% of CDA events overall, but only 38.9% in ApoE4 non-carriers (p=0.045).
• RAW was significantly associated with ApoE4 carriage in the whole sample (HR=3.33, p=0.002) and in patients experiencing relapses (HR=3.60, p=0.002).

Conclusions:

• The study highlights the significant role of genetic factors, specifically the ApoE4 allele, in multiple sclerosis pathogenesis.
• ApoE4 carriage is associated with an increased risk of relapse-associated worsening (RAW) in MS patients.
• Identifying genetic markers like ApoE4 can elucidate MS damage mechanisms and potentially reveal novel therapeutic targets.