Lipoproteins and apolipoproteins in human cerebrospinal fluid. A new role of lipoprotein(a) and apolipoprotein(a) in the neurological diseases characterized by blood-cerebrospinal fluid barrier dysfunction.

The barrier between blood and CSF contributes to homeostasis of the CNS and protects it from potentially harmful substances present in the blood. Lipoproteins present in the CSF are clearly distinct from their plasma counterparts. Human CSF lipoproteins contain mainly Apo AI and Apo E, the former deriving mostly from plasma after crossing the blood-cerebrospinal fluid barrier, the latter being also produced by CNS. Apo AI and E containing lipoproteins in the brain are key players in transport and delivery of lipids, cholesterol homeostasis, and are also involved in CNS remodeling mechanisms. On the other hand, the isoform apo E4 represents the most important genetic risk factor for sporadic and familial late-onset Alzheimer's disease and is involved in brain injury and neurodegenerative diseases. Apo B containing lipoproteins are not produced by CNS and the characterization of normal human CSF lipoproteins did not allowed the isolation of low density lipoproteins.Lipoprotein(a) is a low density lipoprotein-like particle with the unique protein apo(a), which is characterized by a dimensional polymorphism. Lipoprotein(a) is a well known risk factor for athero-thrombosis. The pathological role of Lipoprotein(a) is strictly associated with its plasma concentrations and the size of apo(a) isoforms, with inverse relation. The pathophysiology of Lipoprotein(a) in cardio and cerebrovascular system is widely studied. Recently, we demonstrated that, in neuroinflammatory and neurodegenerative disorders, Lipoprotein(a) can cross a dysfunctional blood-CSF barrier and be found in the CSF. This chapter focuses on the physiological presence of the lipoproteins in CNS, on the pathological aspects deriving from their isoforms, and in particular on the anomalous presence in CSF of Lipoprotein(a).