Immunohistochemical study of distribution of apolipoproteins E and D in human cerebral β amyloid deposits

Navarro, Ana; Valle, Eva del; Astudillo, Aurora; Rey, Carmen González del; Tolivia, Jorge

doi:10.1016/s0014-4886(03)00315-7

Cited by 54 publications

(44 citation statements)

References 43 publications

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“…3. Protective Effect of Apo E-Containing Glial Lipoproteins on Neurons and brain of elderly and AD patients, [154][155][156][157] independently of the amount of apo E. 85) An immunohistochemical study shows that apo E is co-localized with the amyloid core, but apo D is detected around and near the plaques, 158) indicating that apo D might have a role in Ab deposition independent of apo E. Several studies have demonstrated that polymorphisms in the apo D gene are associated with an increase of the risk of AD in Chinese, Finnish and African-American subjects. [159][160][161] Apo AI deficiency in a mouse model of AD (APP V717F) reduced plasma and brain cholesterol levels but not AD pathology in the brain.…”

Section: Lipid Metabolism and Admentioning

confidence: 99%

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Hayashi

2011

Biological & Pharmaceutical Bulletin

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INTRODUCTIONFunctions of the central nervous system (CNS) are performed mainly by neurons and glia-primarily astrocytes, microglia and oligodendrocytes. It has been thought for a long time that glia only passively support neurons, but we now know that glia actively attend to assist in neuronal functions like synaptogenesis and neurotransmission. 1) Although it was believed that ca. 90% of the cells in the brain are glia and the rest of cells are neurons, Azevedo et al. recently reported that the numbers of neurons and non-neuronal cells (glia) are close to equal in human adult brain.2) Brain is the most cholesterol-rich organ in the body, and cholesterol metabolism in the CNS is tightly regulated between neurons and glia. [3][4][5][6][7] Imbalances in the metabolism of lipids, especially cholesterol, are closely linked to the development of several neurodegenerative disorders such as Alzheimer's disease, 8,9) Niemann-Pick type C disease 10) and Smith-Lemli Opitz syndrome. 11,12) In this review the regulation of lipid metabolism and the roles of glial lipoproteins in the CNS will be discussed. LIPID HOMEOSTASIS IN THE CNSThe system of lipid metabolism and transport in the CNS is different from that in peripheral tissues because the CNS is segregated from the peripheral circulation by the blood-brain barrier (BBB).13) Although lipoprotein particles can cross the BBB in vivo in Drosophila, which has a functional BBB like that in vertebrates, 14) lipoproteins in the mouse, rat and human do not cross the BBB. Consequently, since labeled cholesterol peripherally administrated was not found in the CNS of mammals, 15,16) cholesterol in the CNS is derived from de novo synthesis inside of the CNS. Furthermore, in the plasma of subjects who had liver transplantation the genotype of apolipoprotein (apo) E was that of the donor, whereas the subjects retained the own apo E genotype in the cerebrospinal fluid (CSF).17) Moreover, lipoproteins in the CNS consist of only high density lipoprotein (HDL)-like particles in contrast to the circulation which contains very low density lipoproteins (VLDL), low density lipoproteins (LDL) and HDL. It is known that the HDL-like particles in the CNS are secreted from glia (glial lipoproteins), mainly astrocytes and microglia, under normal conditions, [18][19][20] however lipoproteins can be secreted from neurons in vitro 21,22) and in vivo 23) under some specific conditions. Unesterified cholesterol is the major sterol in the adult brain, and small amounts of desmosterol and cholesteryl ester are also present. The majority (70-80%) of cholesterol in the adult brain is in myelin formed by oligodendrocytes. 24)Thus, the activity of cholesterol synthesis in the CNS is the highest during the myelinogenesis. After myelination, cholesterol synthesis continues at very low level in the CNS, and occurs mainly in astrocytes. 5,13,24) Neurons do not efficiently synthesize cholesterol and rely on external source of cholesterol from astrocytes, 25) so that neurons take up cholesterol as lipoproteins via ...

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Section: Lipid Metabolism and Admentioning

confidence: 99%

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Hayashi

2011

Biological & Pharmaceutical Bulletin

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“…For example, elevated plasma levels of ApoD have been found in the brain and cerebrospinal fluid in patients suffering from Alzheimer's disease. 17,18 Similarly, ApoD has been implicated in psychiatric illnesses, where elevated levels of ApoD have been detected in plasma from drug-naive schizophrenic patients. 19 Furthermore, analyses of post-mortem brains documented increased expression levels of ApoD in patients with bipolar disorder and schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

et al. 2006

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“…The high level expression of apoE in the brain, its presence in the β-amyloid-containing neutritic plaques 5,6 and association of an isoform ε4 of apoE in the pathogenesis of Alzheimer's disease (AD) 7 suggest apoE's role in the pathogenesis of AD. The high avidity binding of apoE to the β-amyloid protein 8 has further established a strong link between brain apoE and AD.…”

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Dietary Cholesterol and Estrogen Administration Elevate Brain Apolipoprotein E in Mice by Different Mechanisms

Srivastava¹,

Averna²,

Srivastava

2008

ANS

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Apolipoprotein (apo) E plays an important role in the whole body cholesterol homeostasis. Recent studies suggest that it may also be involved in the local cholesterol transport in the brain, and influence the pathogenesis of Alzheimer's disease (AD) by interacting with the β-amyloid protein and brain lipoprotein receptors. Since apoE expression is highest in the brain, next only to the liver and associated with the pathogenesis of AD, we hypothesized that dietary and hormonal intervention, known to regulate hepatic apoE expression may also regulate brain apoE and thereby influence local cholesterol transport. To test this hypothesis, groups of male C57BL mice were fed either regular rodent chow or high fat (HF) and high cholesterol enriched diet for 3 weeks. In a separate study, groups of male mice were administered pharmacological doses of 17-β estradiol for 5 consecutive days and sacrificed on the 6 th day. As expected, HF diet elevated liver apoE mRNA and apoE synthesis. Similar to liver, brain apoE mRNA and synthesis also increased, following HF feeding. Estradiol administration increased liver apoE synthesis without affecting apoE mRNA. Interestingly, estradiol administration also increased the brain apoE synthesis, but without altering the brain apoE mRNA. These studies suggested that dietary cholesterol and estrogen administration elevated the brain apoE by different mechanisms.

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Immunohistochemical study of distribution of apolipoproteins E and D in human cerebral β amyloid deposits

Cited by 54 publications

References 43 publications

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

Dietary Cholesterol and Estrogen Administration Elevate Brain Apolipoprotein E in Mice by Different Mechanisms

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