Fig. 2

Factors affecting CSF dynamics in ALS patients. Several components of the glymphatic pathway are potentially disrupted in ALS patients. Ageing, for instance, is linked to reduced vascular pulsation, due to an increase in vessel wall stiffness. ALS patients also tend to suffer from poor sleep and impaired respiratory function, particularly towards later stages of the disease. Impairment of two major drivers of glymphatic influx, coupled to disturbed sleep, could underlie highly reduced glymphatic clearance in ALS patients. Other features of ALS that could impact on glymphatic function include abnormal AQP4 expression, raised norepinephrine levels, and vascular factors, such as hypertension and hypoperfusion. Whilst neuroimaging studies have demonstrated abnormal CSF dynamics in ALS patients, further studies may be required to specifically determine the influence of these different factors on glymphatic clearance in ALS patients