The Interaction of Amyloid-β with ApoE

Carter, Donald B.

doi:10.1007/0-387-23226-5_13

Cited by 65 publications

(49 citation statements)

References 67 publications

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“…Moreover, this transport is affected or even mediated by ApoE, possibly by direct binding of A␤ to ApoE-lipoproteins 59 , facilitating diffusion-mediated drainage, interstitially and/or into the cerebrospinal fluid. Direct A␤ to ApoE lipoprotein interactions occurring during or after co-lateral secretion and reuptake could influence each others fate in terms of diffusion and degradation.…”

Section: Cortical Versus Thalamic Amyloid Pathologymentioning

confidence: 99%

Neuronal or Glial Expression of Human Apolipoprotein E4 Affects Parenchymal and Vascular Amyloid Pathology Differentially in Different Brain Regions of Double- and Triple-Transgenic Mice

Dooren

Muyllaert

Borghgraef

et al. 2006

The American Journal of Pathology

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Apolipoprotein E4 (ApoE4) is associated with Alzheimer's disease by unknown mechanisms. We generated six transgenic mice strains expressing human ApoE4 in combination with mutant amyloid precursor protein (APP) and mutant presenilin-1 (PS1) in single-, double-, or triple-transgenic combinations. Diffuse, but not dense, amyloid plaque-load in subiculum and cortex was increased by neuronal but not glial ApoE4 in old (15 months) double-transgenic mice, whereas both diffuse and dense plaques formed in thalamus in both genotypes. Neuronal and glial ApoE4 promoted cerebral amyloid angiopathy as extensively as mutant PS1 but with pronounced regional differences: cortical angiopathy was induced by neuronal ApoE4 while thalamic angiopathy was again independent of ApoE4 source. Angiopathy correlated more strongly with soluble A␤40 and A␤42 levels in cortex than in thalamus throughout the six genotypes. Neither neuronal nor glial ApoE4 affected APP proteolytic processing, as opposed to mutant PS1. Neuronal ApoE4 increased soluble amyloid levels more than glial ApoE4, but the A␤42/40 ratios were similar, although significantly higher than in single APP transgenic mice. We conclude that although the cellular origin of ApoE4 differentially affects regional amyloid pathology, ApoE4 acts on the disposition of amyloid peptides downstream from their excision from APP but without induction of tauopathy. Alzheimer's disease (AD) is characterized by pathological accumulations in the brain of extracellular amyloid plaques and intraneuronal accumulations of protein tau known as neurofibrillary tangles. The amyloid peptides A␤40 and A␤42 are the major components of the amyloid deposits in parenchyma and vasculature.1 The amyloid peptides are excised from the integral membrane protein amyloid precursor protein (APP) by sequential endoproteolytic cleavages by ␤-and ␥-secretases.2 The exact causes and consequences, in terms of normal processes and mechanisms that are disturbed by the amyloid peptides and causing neurodegeneration, remain primarily unclear. 3Besides APP and presenilins (PS1, PS2), the apolipoprotein E (ApoE) is genetically linked to AD. 4 The ApoE4 lipoprotein or its encoding ⑀4 allele, are epidemiologically associated with AD and confer an increased risk and earlier age of onset relative to the more common ApoE3 protein or ⑀3 allele. [5][6][7] ApoE is a 34-kd protein abundantly expressed in liver and brain. In the circulation, ApoE-lipoproteins mediate transport of lipids and cholesterol from and to liver and extrahepatic tissues. In contrast to the peripheral functions of ApoE that are well understood, details of its actions in the central nervous system remain primarily unknown. Actually, the epidemiological association of the ⑀4-allele to AD provided a strong impetus to research, by pointing out our lack of understanding the physiology of lipid and cholesterol homeostasis and of their transport in brain, in particular the contribution of ApoE and various ApoE receptors. 8,9

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Section: Cortical Versus Thalamic Amyloid Pathologymentioning

confidence: 99%

Neuronal or Glial Expression of Human Apolipoprotein E4 Affects Parenchymal and Vascular Amyloid Pathology Differentially in Different Brain Regions of Double- and Triple-Transgenic Mice

Dooren

Muyllaert

Borghgraef

et al. 2006

The American Journal of Pathology

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“…An obvious fact is that the APOE ε4 allele remains one of the most important genetic risk factors for dementia, especially for the sporadic form of AD [4,7]. Recently, the correlation between the APOE ε4 allele and vascular dementia was demonstrated [7].…”

Section: Introductionmentioning

confidence: 99%

“…The apolipoprotein E gene (APOE) , located on chromosome 19, belongs to the genes increasing the risk of Alzheimer's disease (AD) development [3,4]. Apolipoprotein E (ApoE) is a polymorphic protein occurring in humans in 3 isomorphic forms: ApoE2 (Cys112/Cys158), ApoE3 (Cys112/Arg158) and ApoE4 (Arg112/Arg158), which are coded by 3 allelic sets of the APOE gene (ε2, ε3, ε4).…”

Section: Introductionmentioning

confidence: 99%

Cognitive Function, <b><i>APOE</i></b> Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Bojar¹,

Stasiak²,

Cyniak-Magierska³

et al. 2016

Dement Geriatr Cogn Disord

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Background: The objective of the study was to analyze a potential association between cognitive functions and thyroid status in postmenopausal women with different polymorphisms of the apolipoprotein E gene (APOE). Methods: The examined population included 402 postmenopausal women from south-eastern Poland. The evaluation of cognitive functions was made with the use of the diagnostic Central Nervous System-Vital Signs equipment (Polish version). Multiplex polymerase chain reactions were performed to assess APOE polymorphisms. The thyroid hormone tests were assessed by an accredited laboratory. Results and Conclusion: Lower results of cognitive functions were associated with the presence of the ε4 APOE allele in postmenopausal women. The ε4 APOE polymorphism was associated with a higher concentration of thyroid-stimulating hormone and lower concentrations of free triiodothyronine and total triiodothyronine.

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“…It is interesting to note that apoE has been reported to bind directly to intermediate aggregates or 'oligomers' of the β-amyloid peptide (Aβ) associated with Alzheimer's disease, with apoE4 having the greatest affinity for such binding [27]. Given the fact that Aβ and α-syn both have the ability to form highly similar β-pleated sheet structures, which can even be recognised by the same monoclonal antibody [9], it would not be surprising if apoE also had the ability to bind to oligomeric α-syn.…”

Section: Discussionmentioning

confidence: 99%

Effects of different isoforms of apoE on aggregation of the α‐synuclein protein implicated in Parkinson’s disease

Emamzadeh

Aojula

McHugh

2016

Neuroscience Letters

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Parkinson's disease is a progressive brain disorder due to the degeneration of dopaminergic neurons in the substantia nigra. Parkinson's disease is a progressive brain disorder due to the degeneration of dopaminergic neutrons in the SN. The accumulation of aggregated forms of α-synuclein protein into Lewy bodies is one of the characteristic features of this disease although the pathological role of any such protein deposits in causing neurodegeneration remains elusive. Here, the effects of different apolipoprotein E isoforms (apoE2, apoE3, apoE4) on the aggregation of α-synuclein in vitro were examined using thioflavin T assays and also an immunoassay to detect the formation of multimeric forms.Our results revealed that the aggregation of α-synuclein is influenced by apoE concentration. At low concentrations of apoE (<15 nM), all of the isoforms were able to increase the aggregation of α-synuclein (50 µM), with apoE4 showing the greatest stimulatory effect. This is in contrast to a higher concentration (>15 nM) of these isoforms, where a decrease in the aggregation of α-synuclein was noted. The data show that exceptionally low levels of apoE may seed α-syn aggregation, which could potentially lead to the pathogenesis of α-synuclein-induced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of α-synuclein aggregation and confer protection. The differential effects noted with apoE4 could explain why this particular isoform results in an earlier age of onset for Parkinson's disease.

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The Interaction of Amyloid-β with ApoE

Abstract: Abstract:Brain plaque deposition in the form of amyloid-beta (AP) peptide is a pathological hallmark of Alzheimer's disease (AD

Cited by 65 publications

References 67 publications

Neuronal or Glial Expression of Human Apolipoprotein E4 Affects Parenchymal and Vascular Amyloid Pathology Differentially in Different Brain Regions of Double- and Triple-Transgenic Mice

Neuronal or Glial Expression of Human Apolipoprotein E4 Affects Parenchymal and Vascular Amyloid Pathology Differentially in Different Brain Regions of Double- and Triple-Transgenic Mice

Cognitive Function, <b><i>APOE</i></b> Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Effects of different isoforms of apoE on aggregation of the α‐synuclein protein implicated in Parkinson’s disease

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