A mathematical model for the evaluation of iron transport across the blood-cerebrospinal fluid barrier in neurodegenerative diseases

Iron plays important roles in healthy brain but altered homeostasis and concentration have been correlated to aging and neurodegenerative diseases. Iron enters the central nervous system by crossing the brain barrier systems: the Blood- Brain Barrier separating blood and brain and the Blood-Cerebrospinal Fluid Barrier (BCSFB) between blood and CSF, which is in contact with the brain by far less selective barriers. Herein, we develop a two-compartmental model for the BCSFB, based on first-order ordinary differential equations, performing numerical simulations and sensitivity analysis. Furthermore, as input parameters of the model, experimental data from patients affected by Alzheimer's disease, frontotemporal dementia, mild cognitive impairment and matched neurological controls were used, with the aim of investigating the differences between physiological and pathological conditions in the regulation of iron passage between blood and CSF which can be possibly targeted by therapy.