Brain lipoprotein metabolism and its relation to neurodegenerative disease

Lipoproteins are macromolecular complexes composed of lipids and proteins. The role of these complexes is to provide cells of the organism with lipids to be used as a source of energy, building blocks for biomembrane synthesi s, and lipophilic molecules (e.g., steroid hormones and vitamin E) for othe r physiological purposes, such as cell signaling and antioxidative mechanis ms. Lipoproteins also promote the cellular afflux of cholesterol fur its di sposal into bile. Thus, lipoproteins play an important role in the maintena nce of lipid homeostasis throughout the organism. Accordingly, lipoprotein particles have been found circulating in blood, lymph, and interstitial flu id. Despite the existence of the blood-brain barrier, lipoprotein particles have been shown to be also present in the cerebrospinal fluid (CSF). Altho ugh a portion of their protein components may filter through the barrier fr om the vascular compartment, experimental evidence indicates that these par ticles originate from the nervous tissue. The other protein components incl ude apolipoproteins E, J, and D, and these have been shown to be synthesize d by cells within the central nervous system (CNS). Furthermore, it was sho wn that lipoprotein particles can be isolated from the conditioned medium o f astrocytic cultures. The differences in size, structure, and composition of in vitro assembled particles compared with those isolated from the CSF s uggest that the particles are modified following their secretion in vivo. T his is supported by observations that lipoprotein-modifying enzymes and tra nsfer proteins are also present within CNS tissue and CSF. The fate of CSF lipoproteins is unclear but is probably related to the turnover and clearan ce of lipids from the CNS or, alternatively, the particles may be recapture d and recycled back into the CNS tissue. The presence of several cell surfa ce receptors for apoE-containing lipoproteins on ependymal cells, as well a s on neurons and glial cells, supports this notion and suggests that the is olated brain possesses its own system to maintain local lipid homeostasis. This is further exemplified by the salvage and recycling of lipids shown to occur following a lesion in order to allow surviving neurons to sprout and reestablish lost synapses. Not much is currently known about lipoprotein m etabolism in neurodegenerative diseases, but lipid alterations have been re peatedly reported in Alzheimer brains in which neuronal loss and deafferent ation are major features. Although the mechanism underlying the link betwee n the epsilon 4 allele of the apolipoprotein E gene and Alzheimer's disease is presently unclear, it may well be postulated that it is related to dist urbances in brain lipoprotein metabolism.