Implication of Central Nervous System Barrier Impairment in Amyotrophic Lateral Sclerosis: Gender-Related Difference in Patients

Abstract

Central nervous system (CNS) barrier impairment has been reported in amyotrophic lateral sclerosis (ALS), highlighting its potential significance in the disease. In this context, we aim to shed light on its involvement in the disease, by determining albumin quotient (QAlb) at the time of diagnosis of ALS in a large cohort of patients. Patients from the university hospital of Tours (n = 307) were included in this monocentric, retrospective study. In total, 92 patients (30%) had elevated QAlb levels. This percentage was higher in males (43%) than in females (15%). Interestingly, QAlb was not associated with age of onset, age at sampling or diagnostic delay. However, we found an association with ALS functional rating scale-revised (ALSFRS-r) at diagnosis but this was significant only in males. The QAlb levels were not linked to the presence of a pathogenic mutation. Finally, we performed a multivariate survival analysis and found that QAlb was significantly associated with survival in male patients (HR = 2.3, 95% CI = 1.2–4.3, p = 0.009). A longitudinal evaluation of markers of barrier impairment, in combination with inflammatory biomarkers, could give insight into the involvement of CNS barrier impairment in the pathogenesis of the disease. The gender difference might guide the development of new drugs and help personalise the treatment of ALS.

Associations of cerebrospinal fluid profiles with severity and mortality risk of amyotrophic lateral sclerosis

“…Q ALB is recognized as an effective marker to evaluate the permeability of the BBB ( Reiber and Peter, 2001 ). The current finding of the significant increase in Q ALB of ALS patients was consistent with some studies ( Wu et al, 2020 ; Alarcan et al, 2023 ). Some researchers believed that the disruption of BBB was an early event in ALS, and most studies suggested that BBB disruption in neurodegenerative diseases mediates the invasion of immune cells from the blood, resulting in neurodegeneration ( Aragón-González et al, 2022 ; Beaman et al, 2022 ).…”