Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

Lane, Roger; Farlow, Martin R.

doi:10.1194/jlr.m400486-jlr200

Cited by 157 publications

(133 citation statements)

References 239 publications

(243 reference statements)

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“…That may account for the decline in cognitive function [33]. Furthermore, individuals carrying the apolipoprotein E (APOE) epsilon four allele, and particularly those with both APOE and BChE K-variant alleles, have the fastest cognitive decline among subjects with amnestic mild cognitive impairment, mild AD and the slowest decline in more advanced stages of the illness [34][35][36]. Then, insulin resistance concomitant with elevated BChE activity may play the synergic effect of cardiovascular diseases and the impairment of memory function in the future.…”

Section: Discussionmentioning

confidence: 99%

Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels

et al. 2014

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Abdominal obesity (AO) has a strong correlation with cardiovascular disease and has been linked to Alzheimer's disease and type 2 diabetes. We investigated the association between AO and elevated serum butyrylcholinesterase (BChE) activity, insulin resistance and the serum lipid profile, including triglyceride (TG), HDLcholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels in AO and non-AO women subjects. A total of 500 AO subjects (age 49.1 ± 10.5 years), and 142 non-AO women subjects (age 49.9 ± 11.9 years) were enrolled for the general biochemistry tests, serum BChE, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Body mass index, waist circumference, Blood pressure (BP), plasma glucose (Glu), triglyceride (TG), BChE, insulin, HOMA-IR were significantly higher and HDL-C levels were significantly lower in AO subjects (p \ 0.05). Waist circumference was significantly correlated with BP, Glu, TG, BChE, insulin and HOMA-IR in AO subjects. Multiple logistic regression demonstrated that AO was associated with elevated BChE, HOMA-IR, hypertension and reduced HDL-C after adjusting for these variables. AO is associated with elevated BChE, insulin resistance, HT and reduced HDL-C. These may predict the development of type 2 diabetes mellitus and may be associated with cognitive disorder in the future, both are mediated through insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels

et al. 2014

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“…Similar to LXR-α mRNA, the strongest induction of LXR-β mRNA occurred in the heart of diabetic rats, which showed a 1.18-fold increase compared with control rats. It is generally accepted that ApoE, the main apolipoprotein in the brain, is crucial for brain cholesterol homeostasis [18][19][20][21] . The levels of ApoE mRNA in the indicated tissues were measured, and the results showed a high expression of ApoE mRNA in the liver, hippocampus and cerebral cortex ( Figure 3C).…”

Section: Resultsmentioning

confidence: 99%

“…It is not clear what mechanisms are responsible for increasing the FC levels in the hippocampus and cerebral cortex. ApoE is considered to be a major apolipoprotein for cholesterol transport and clearance in the brain [18][19][20][21] . The data from QT-PCR showed that apart from the liver, the peripheral tissues exhibited a low level of ApoE mRNA, which was in accordance with the fact that the liver is the primary organ for ApoE secretion [29] .…”

Section: Discussionmentioning

confidence: 99%

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Wang

Liu

et al. 2012

Acta Pharmacol Sin

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Aim: Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions. The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications. Methods: Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats. On d 35 after the injection, liver, heart, intestine, kidney, pancreas, cerebral cortex and hippocampus were isolated from the rats. The content of total and free cholesterol in the tissues was determined using HPLC. The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses, respectively. Results: In diabetic rats, the level of free cholesterol was significantly decreased in the peripheral tissues, but significantly elevated in hippocampus, as compared with those in the control rats. Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues, but significant change was only found in kidney and liver. In diabetic rats, the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex, but the change had no statistical significance. Conclusion: Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus. The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.

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“…ApoE is a cholesterol transporter: the ApoE4 isoform binds preferably to LDL and VLDL cholesterol while ApoE2 and ApoE3 bind preferably to HDL cholesterol (Lane and Farlow, 2005). ApoE isoforms influence the composition of membrane lipid rafts and delivery of essential fatty acids such as DHA to neurons (Lane and Farlow, 2005). In particular, ApoE can coordinate the mobilization of cholesterol for maintenance and repair of neuron membranes (Poirier, 2003).…”

Section: Apoe Gene and Apolipoprotein Ementioning

confidence: 99%

“…ApoE3 is the most common isoform. ApoE is a cholesterol transporter: the ApoE4 isoform binds preferably to LDL and VLDL cholesterol while ApoE2 and ApoE3 bind preferably to HDL cholesterol (Lane and Farlow, 2005). ApoE isoforms influence the composition of membrane lipid rafts and delivery of essential fatty acids such as DHA to neurons (Lane and Farlow, 2005).…”

Section: Apoe Gene and Apolipoprotein Ementioning

confidence: 99%

Long-chain omega3 polyunsaturated fatty acids and cognition in older people: interaction with APOE genotype

Barberger‐Gateau

Samieri

Cunnane³

2015

OCL

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-Basic research and epidemiological studies suggest a protective effect of long-chain omega3 polyunsaturated fatty acids (LC n-3 PUFA) against age-related cognitive decline. However, most randomized controlled trials with LC n-3 PUFA supplements have yielded disappointing results on cognitive outcomes in older persons. One explanation for this discrepancy may be an inadequate targeting of potential beneficiaries of LC n-3 PUFA according to their Apolipoprotein E (APOE) genotype. The aim of this paper was to examine the potential modifying effect of APOE genotype on LC n-3 PUFA metabolism and its relation to cognitive decline in older persons. At least five epidemiological studies and three intervention studies with LC n-3 PUFA supplements have found an interaction between LC n-3 PUFA and APOE genotype on cognition. However, the direction of the effect is inconsistent across studies: the impact of LC n-3 PUFA on cognition is stronger in APOE4 carriers (the main genetic risk factor for Alzheimer's disease) in some studies, but conversely stronger in APOE4 non-carriers in other studies. These discordant results may be explained by different age groups, cognitive status, measures of cognition, or amounts of DHA intake across studies. Experimental studies suggest that the APOE4 genotype modifies the metabolism of DHA. The APOE genotype should be systematically taken into account and interactions tested in epidemiological and intervention studies with LC n-3 PUFA. Further research is needed to better understand the underlying mechanisms of this gene X diet interaction.Keywords: Cognition / aging / omega3 fatty acids / Apolipoprotein E gene / DHA Résumé -Acides gras oméga-3 à longue chaîne et cognition chez les sujets âgés : interaction avec le géno-type APOE. La recherche fondamentale et les études épidémiologiques suggèrent un effet protecteur des acides gras oméga3 à longue chaîne (AGPI-LC n-3) contre le déclin cognitif lié à l'âge. Cependant les études d'intervention avec des suppléments d'AGPI-LC n-3 ont donné des résultats décevants sur la cognition. Une raison pourrait en être un ciblage inadéquat des bénéficiaires potentiels d'une supplémentation en raison notamment de leur génotype pour le gène de l'Apolipoprotéine E (APOE). L'objectif de cet article était d'explorer l'effet potentiellement modificateur du géno-type de l'APOE sur le métabolisme des AGPI-LC n-3 et sa relation avec le déclin cognitif chez le sujet âgé. Au moins cinq études épidémiologiques et trois études d'intervention ont mis en évidence une interaction entre les AGPI-LC n-3 et le génotype de l'APOE sur la cognition des personnes âgées. Cependant la direction de l'effet est inconstant entre les études, certaines montrent un impact des AGPI-LC n-3 uniquement chez les porteurs de l'allèle epsilon4 (APOE4), principal facteur de risque génétique de maladie d'Alzheimer, et d'autres inversement un effet chez les non-porteurs de l'APOE4. Ces résultats discordants peuvent s'expliquer par des différences d'âge, de statut cognitif, de domaine d...

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Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

Cited by 157 publications

References 239 publications

Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels

Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats

Long-chain omega3 polyunsaturated fatty acids and cognition in older people: interaction with APOE genotype

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