Elevated Low-Density Lipoprotein in Alzheimer's Disease Correlates with Brain Aβ 1–42 Levels

Kuo, Yu Min; Emmerling, Mark R.; Bisgaier, Charles L.; Essenburg, Arnold D.; Lampert, Heather C.; Drumm, Denise A.; Roher, Alex E.

doi:10.1006/bbrc.1998.9652

Cited by 305 publications

(224 citation statements)

References 35 publications

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“…Since approximately 90% of ApoB in plasma is normally bound to LDL, it is not surprising that the highest ApoB levels were detected among APOE ɛ 4 allele carriers. Interestingly though, increased levels of serum ApoB have been shown to correlate with A β 42 levels in the brain and increased serum ApoB levels have been reported among AD patients 31, 32. Accordingly, previous studies utilizing transgenic AD mouse models have shown that the overexpression of human ApoB promotes memory decline and increases lipid peroxidation, A β load, neurodegeneration, and astrogliosis in the brain 33, 34.…”

Section: Discussionmentioning

confidence: 99%

Decreased plasma C‐reactive protein levels in APOE ε4 allele carriers

Martiskainen

Takalo

Solomon

et al. 2018

Ann Clin Transl Neurol

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ObjectiveApolipoprotein E (APOE) ε4 allele is a well‐established risk factor in Alzheimer's disease (AD). Here, we assessed the effects of APOE polymorphism on cardiovascular, metabolic, and inflammation‐related parameters in population‐based cohorts.MethodsAssociation of cardiovascular, metabolic, and inflammation‐related parameters with the APOE polymorphism in a large Finnish Metabolic Syndrome in Men (METSIM) cohort and Finnish Geriatric Intervention study to prevent cognitive impairment and disability (FINGER) were investigated. Brain‐specific effects were addressed in postmortem brain samples.ResultsIndividuals carrying the APOE ε4 allele displayed significantly elevated serum/plasma LDL cholesterol and apolipoprotein B levels. APOE ε3ε4 and ε4ε4 significantly associated with lower levels of plasma high‐sensitivity C‐reactive protein (hs‐CRP). Plasma amyloid‐β 42 (Aβ42) and reduced hs‐CRP levels showed an association independently of the APOE status.InterpretationThese data suggest that the APOE ε4 allele associates with lower levels of hs‐CRP in individuals without dementia. Moreover, Aβ42 may encompass anti‐inflammatory effects reflected by reduced hs‐CRP levels.

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Section: Discussionmentioning

confidence: 99%

Decreased plasma C‐reactive protein levels in APOE ε4 allele carriers

Martiskainen

Takalo

Solomon

et al. 2018

Ann Clin Transl Neurol

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“…ApoE4 is a genetic predisposing factor in AD. Serum apoB levels are increased in AD (115,116), and although predominantly a serum protein, apoB is also found in hippocampus, where it is associated with hippocampal amyloid deposits and neurofibrillary tangles (117). Overexpression of apoB in mice increases APP expression in mice fed a high cholesterol diet (118).…”

Section: Discussionmentioning

confidence: 99%

Protection against β-Amyloid-induced Apoptosis by Peptides Interacting with β-Amyloid

Nelson

Alkon

2007

Journal of Biological Chemistry

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␤-Amyloid peptide produces apoptosis in neurons at micromolar concentrations, but the mechanism by which ␤-amyloid exerts its toxic effect is unknown. The normal biological function of ␤-amyloid is also unknown. We used phage display, coprecipitation, and mass spectrometry to examine the proteinprotein interactions of ␤-amyloid in normal rabbit brain in order to identify the biochemical receptors for ␤-amyloid. ␤-Amyloid was found to bind primarily to proteins involved in low density lipoprotein and cholesterol transport and metabolism, including sortilin, endoplasmic reticulum-Golgi intermediate compartment 2 (ERGIC2), ERGIC-53, steroid 5␣-reductase, and apolipoprotein B. ␤-Amyloid also bound to the C-reactive protein precursor, a protein involved in inflammation, and to 14-3-3, a protein that regulates glycogen synthase kinase-3␤, the kinase involved in tau phosphorylation. Of eight synthetic peptides identified as targets of ␤-amyloid, three were found to be effective blockers of the toxic effect of ␤-amyloid on cultured neuronal cells. These peptides bound to the hydrophobic region (residues 17-21) or to the nearby protein kinase C pseudo-phosphorylation site (residues 26 -30) of ␤-amyloid, suggesting that these may be the most critical regions for ␤-amyloid effector action and for aggregation. Peptides or other small molecules that bind to this region may protect against ␤-amyloid toxic effect by competitively blocking its ability to bind ␤-amyloid effector proteins such as sortilin and 14-3-3.

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“…Besides increasing the risk of cardiovascular disease with subsequent increased risks of cognitive decline, high cholesterol levels might also directly influence the risk of cognitive decline. High total serum cholesterol levels have been shown to associate with lower cerebral spinal fluid levels of b-amyloid and larger amounts of b-amyloid deposition in brain autopsy studies [9,10].…”

Section: Introductionmentioning

confidence: 99%

Pravastatin and cognitive function in the elderly. Results of the PROSPER study

et al. 2009

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Observational studies have given conflicting results about the effect of statins in preventing dementia and cognitive decline. Moreover, observational studies are subject to prescription bias, making it hard to draw definite conclusions from them. Randomized controlled trials are therefore the preferred study design to investigate the association between statins and cognition. Here we present detailed cognitive outcomes from the randomized placebocontrolled PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cognitive function was assessed repeatedly in all 5,804 PROSPER participants at six different time points during the study using four neuropsychological performance tests. After a mean follow-up period of 42 months, no difference in cognitive decline at any of the cognitive domains was found in subjects treated with pravastatin compared to placebo (all p [ 0.05). Pravastatin treatment in old age did not affect cognitive decline during a 3 year follow-up period. Employing statin therapy in the elderly in an attempt to prevent cognitive decline therefore seems to be futile.

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Elevated Low-Density Lipoprotein in Alzheimer's Disease Correlates with Brain Aβ 1–42 Levels

Cited by 305 publications

References 35 publications

Decreased plasma C‐reactive protein levels in APOE ε4 allele carriers

Decreased plasma C‐reactive protein levels in APOE ε4 allele carriers

Protection against β-Amyloid-induced Apoptosis by Peptides Interacting with β-Amyloid

Pravastatin and cognitive function in the elderly. Results of the PROSPER study

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