Journal of Lipid Research
Volume 45, Issue 8, August 2004, Pages 1375-1397
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Thematic Review
Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal

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Unesterified cholesterol is an essential structural component of the plasma membrane of every cell. During evolution, this membrane came to play an additional, highly specialized role in the central nervous system (CNS) as the major architectural component of compact myelin. As a consequence, in the human the mean concentration of unesterified cholesterol in the CNS is higher than in any other tissue (∼23 mg/g). Furthermore, even though the CNS accounts for only 2.1% of body weight, it contains 23% of the sterol present in the whole body pool. In all animals, most growth and differentiation of the CNS occurs in the first few weeks or years after birth, and the cholesterol required for this growth apparently comes exclusively from de novo synthesis. Currently, there is no evidence for the net transfer of sterol from the blood into the brain or spinal cord. In adults, the rate of synthesis exceeds the need for new structural sterol, so that net movement of cholesterol out of the CNS must take place. At least two pathways are used for this excretory process, one of which involves the formation of 24(S)-hydroxycholesterol.

Whether or not changes in the plasma cholesterol concentration alter sterol metabolism in the CNS or whether such changes affect cognitive function in the brain or the incidence of dementia remain uncertain at this time.

Alzheimer's disease
amyloid precursor protein
oxysterols
dementia
amyloid β peptide
blood-brain barrier
apolipoprotein E
apolipoprotein A-I
lipoprotein transporters
ATP binding cassette transporters

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Published, JLR Papers in Press, May 16, 2004. DOI 10.1194/jlr.R400004-JLR200

    Abbreviations

    ABC

    ATP binding cassette

    apoE

    apolipoprotein E

    CNS

    central nervous system

    kcal

    kilocalories

    LDL-C

    cholesterol carried in low density lipoprotein

    LDLR

    LDL receptor

    LRP

    LDLR-related protein

    LXRβ

    liver X receptor-β

    NPC1

    Niemann-Pick C1

    NPC2

    Niemann-Pick C2

    NPC1L1

    Niemann-Pick C1-like 1

    PNS

    peripheral nervous system

    SR-BI

    scavenger receptor class B type I

    SREBP

    sterol-regulatory element binding protein

    TC

    total cholesterol