Cholesteryl ester transfer protein polymorphism D442G associated with a potential decreased risk for Alzheimer's disease as a modifier for APOE ε4 in Chinese

Chen, Dawei; Yang, Jiao; Tang, Zhe; Xiu-min, Dong; Feng, Xiaoyan; Yu, Shun; Chan, Piu

doi:10.1016/j.brainres.2007.10.054

Cited by 27 publications

(20 citation statements)

References 23 publications

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“…Prior studies found similar effects using comparably sized, and even smaller (Chen et al 2008), samples. Given the data currently available, this study was limited to a restricted exploratory analysis for subtle effects using relaxed correction for multiple comparisons.…”

Section: Discussionmentioning

confidence: 60%

“…One study of 286 AD subjects found that risk of AD was lower in carriers of APOE ε4 with the C-629A AA genotype (Rodríguez et al 2006), and another study of 544 AD subjects reported that risk of AD was higher in non-carriers of APOE ε4 with the I405V VV genotype (Arias-Vásquez et al 2007), analogous to the present finding that the I allele was protective in non-carriers. The finding of alleles that lower CETP levels being protective in APOE ε4 carriers is further supported by a study of 107 AD subjects in which another CETP polymorphism, D442G, was associated with lower levels of CETP and decreased risk of AD in APOE ε4 carriers (Chen et al 2008). …”

Section: Discussionmentioning

confidence: 81%

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CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer’s disease risk in an APOE-dependent manner

Murphy

Roddey²,

McEvoy

et al. 2011

Brain Imaging and Behavior

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Two alleles in cholesteryl ester transfer protein (CETP) gene polymorphisms have been disputably linked to enhanced cognition and decreased risk of Alzheimer’s disease (AD): the V and A alleles of I405V and C-629A. This study investigates whether these polymorphisms affect brain structure in 188 elderly controls and 318 AD or mild cognitive impairment (MCI) subjects from the Alzheimer’s Disease Neuroimaging Initiative cohort. Nominally signficant associations were dependent on APOE ε4 carrier status. In APOE ε4 carriers, the V and A alleles, both of which decrease CETP and increase HDL, associated with greater baseline cortical thickness and less 12-month atrophy in the medial temporal lobe. Conversely, in APOE ε4 non-carriers, the I allele, which increases CETP and decreases HDL, associated with greater baseline thickness, less atrophy and lower risk of dementia. These results suggest CETP may contribute to the genetic variability of brain structure and dementia susceptibility in an APOE-dependent manner.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 81%

CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer’s disease risk in an APOE-dependent manner

Murphy

Roddey²,

McEvoy

et al. 2011

Brain Imaging and Behavior

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show abstract

“…A study with a Northern Han-Chinese population showed that the frequency of the DG genotype or the G allele of the CETP D442G polymorphism was greater in control subjects than in AD patients. These results suggest that the G allele may have a potential protective effect against the development of AD, especially in APOE epsilon4 carriers (66).…”

Section: Alzheimer's Disease Riskmentioning

confidence: 76%

“…Ha and Barter (3) reported that CETP is present in fish, reptiles, birds, and mammals, but not in rats and mice. Chemical purification showed that CETP is a plasma glycoprotein consisting of 476 amino acids with an apparent molecular weight of [66][67][68][69][70][71][72][73][74]. This discovery led to subsequent cDNA cloning and tissue expression studies (5).…”

Section: Brief Highlights Of Cetp Historymentioning

confidence: 99%

Cholesteryl ester transfer protein: The controversial relation to atherosclerosis and emerging new biological roles

Oliveira

Faria

2011

IUBMB Life

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SummaryCholesteryl ester transfer protein (CETP) exerts a profound impact on high-density lipoprotein (HDL) metabolism and, consequently, on the risk of atherosclerosis development and cardiovascular mortality. Here, we review the complex relationship between CETP and atherosclerosis based upon the experimental, clinical, and epidemiological studies. In addition, we discuss the recent findings that expand the functions of CETP to new areas of interest such as Alzheimer's disease, inflammation, and obesity.

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“…14 Inversely, CETP polymorphisms resulting in low HDL-C are prevalent in AD. 15 However, none of these studies infers causality because, as Singh-Manoux et al rightly point out, 11 plasma lipid levels can be considerably modified over the development of dementia, making the time point of the measurement critically important.…”

Section: See Accompanying Article On Page 1556mentioning

confidence: 99%

HDL: Close to Our Memories?

Kontush

Chapman

2008

ATVB

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T he last decade has witnessed an explosion in studies of the role of lipoproteins in brain function. Neurons require a continuous supply of lipids for membrane synthesis and acetylcholine production. Indeed, the brain is a site of intense lipid turnover-even though the central nervous system (CNS) accounts for only 2.1% of body weight, it contains 23% of total body cholesterol. 1 Lipid metabolism in the brain is tightly controlled locally, as plasma lipoproteins are shielded from the brain by the blood-brain barrier. Although neuronal cells are capable of de novo synthesis of a wide spectrum of molecular species of lipids, they rely heavily on exogenous sources and readily bind and internalize lipoproteins of the extracellular fluid. 2 Equally, neurons need to dispose of excess lipids; lipoprotein-mediated lipid transport is therefore bidirectional and includes cellular efflux of cholesterol. 3 See accompanying article on page 1556Human cerebrospinal fluid (CSF) primarily contains spherical lipoproteins of approximately 10 to 12 nm in diameter with hydrated density in the range 1.063 to 1.25 g/mL, thereby resembling HDL in human plasma. 3,4 Lipid concentrations in CSF are however much lower (eg, 300-to 400-fold for total cholesterol and phospholipids) as compared to the plasma compartment. 4 Apolipoproteins (apo) E and A-I are the major apolipoproteins in human CSF (typical concentration range: 0.1 to 0.4 mg/dL 3,4 ), with apoA-II, A-IV, J, D, C-II, C-III, C-IV, and H equally present. 3,4 Importantly, CSF lipoproteins carry amyloid-␤ (A␤), a 39-to 43-aa peptide produced in neuronal cells, which is the major component of senile amyloid plaques. 5 The metabolism of CSF lipoproteins remains poorly characterized but seems to be distinct from that of plasma lipoproteins. ApoE-rich HDL are synthesized locally in CNS and secreted by astrocytes as discoidal complexes enriched in free cholesterol. 6 High apoE content targets these lipoproteins to cellular apoE receptors, particularly LDL receptor-related protein, which is abundantly expressed on the surface of neurons. 2 By contrast, apoA-I-rich CSF lipoproteins are most probably derived from plasma HDL that enter the CNS by crossing the blood-brain barrier, 7 as apoA-I is not synthesized in the CNS. 2 Similar to plasma HDL, CSF lipoproteins can be remodeled by lecithin-cholesterol acyltransferase and phospholipid transfer protein; by contrast, cholesteryl ester transfer protein (CETP) is absent from CSF. 3 These data clearly demonstrate that brain HDL constitute a key element of cholesterol homeostasis in the CNS.Over the past decade, abnormalities in brain lipid metabolism are increasingly recognized to be intimately related to the pathogenesis of such major neurodegenerative disorders as Alzheimer disease (AD) and vascular dementia (VD). With respective frequencies of 70% and 15% of all dementias, AD and VD are the most common forms of dementia which are typically preceded by less dramatic cognitive decline, including decline in memory. 8 Both AD and atherosclerosis ...

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Cholesteryl ester transfer protein polymorphism D442G associated with a potential decreased risk for Alzheimer's disease as a modifier for APOE ε4 in Chinese

Cited by 27 publications

References 23 publications

CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer’s disease risk in an APOE-dependent manner

CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer’s disease risk in an APOE-dependent manner

Cholesteryl ester transfer protein: The controversial relation to atherosclerosis and emerging new biological roles

HDL: Close to Our Memories?

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