title: HDL and cholesterol handling in the brain.
abstract: Cholesterol is an essential component of both the peripheral nervous system and central nervous system (CNS) of mammals. Brain cholesterol is synthesized in situ by astrocytes and oligodendrocytes and is almost completely isolated from other pools of cholesterol in the body, but a small fraction can be taken up from the circulation as 27-hydroxycholesterol, or via the scavenger receptor class B type I. Glial cells synthesize native high-density lipoprotein (HDL)-like particles, which are remodelled by enzymes and lipid transfer proteins, presumably as it occurs in plasma. The major apolipoprotein constituent of HDL in the CNS is apolipoprotein E, which is produced by astrocytes and microglia. Apolipoprotein A-I, the major protein component of plasma HDL, is not synthesized in the CNS, but can enter and become a component of CNS lipoproteins. Low HDL-C levels have been shown to be associated with cognitive impairment and various neurodegenerative diseases. On the contrary, no clear association with brain disorders has been shown in genetic HDL defects, with the exception of Tangier disease. Mutations in a wide variety of lipid handling genes can result in human diseases, often with a neuronal phenotype caused by dysfunctional intracellular lipid trafficking.
authors.affiliation: Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vitali
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Wellington
authors.affiliation: Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy laura.calabresi@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Calabresi
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D010641:Phenotype; D012307:Risk Factors
chemical_list: D001053:Apolipoproteins; D008076:Cholesterol, HDL
keywords: Alzheimer disease; Apolipoprotein E; Central nervous system; High-density lipoproteins; Parkinson disease