Single-molecule imaging of amyloid-beta protein (Abeta) of Alzheimer's disease: from single-molecule structures to aggregation mechanisms and membrane interactions

Marie Isabel Aguilar, Xu Hou, Dusan Losic, Adam Istvan Mechler, Lisandra Lorraine Martin, David Small

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

Abstract

Alzheimer s disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment [1]. The primary neuropathologic feature of AD is the presence, in the brain, of amyloid plaques that are formed by aggregation of the ?-amyloid protein (A?) [2]. A?, containing 39 to 42 amino acids, is derived from proteolysis of the amyloid precursor protein (APP) [3]. Much evidence points to A? as the causative factor for the pathogenesis of AD [4?6]. However, the precise mechanism by which A? induces AD-associated neurotoxicity remains elusive. Some in vitro and ex vivo studies show that, rather than the mature A? amyloid fibrils, it is the soluble low- molecular-weight A? oligomers ? which form at the early stage of aggregation ? that cause the neurotoxic effects in AD [7?9]. Alternatively, rather than A? itself, it has been suggested that the process of aggregation induces AD-associated neurotoxicity [10]. On the other hand, interactions with the plasma membrane have been shown to play an important role in the process of A? misfolding and ultimately aggregation [11?16]. Therefore, determination of the three-dimensional structures of A? in different forms (monomers, oligomers, protofibrils and mature fibrils) and characterization of the misfolding and aggregation mechanisms of A? are needed for an understanding of the pathogenesis of AD.........
Original languageEnglish
Title of host publicationBio-nanoimaging Protein Misfolding and Aggregation
EditorsVladimir N Uversky, Yuri L Lyubchenko
Place of PublicationUK
PublisherAcademia Press
Pages47-56
Number of pages10
Edition1st
ISBN (Print)9780123944313
DOIs
Publication statusPublished - 2014

Cite this

Aguilar, M. I., Hou, X., Losic, D., Mechler, A. I., Martin, L. L., & Small, D. (2014). Single-molecule imaging of amyloid-beta protein (Abeta) of Alzheimer's disease: from single-molecule structures to aggregation mechanisms and membrane interactions. In V. N. Uversky, & Y. L. Lyubchenko (Eds.), Bio-nanoimaging Protein Misfolding and Aggregation (1st ed., pp. 47-56). UK: Academia Press. https://doi.org/10.1016/B978-0-12-394431-3.12001-2
Aguilar, Marie Isabel ; Hou, Xu ; Losic, Dusan ; Mechler, Adam Istvan ; Martin, Lisandra Lorraine ; Small, David. / Single-molecule imaging of amyloid-beta protein (Abeta) of Alzheimer's disease: from single-molecule structures to aggregation mechanisms and membrane interactions. Bio-nanoimaging Protein Misfolding and Aggregation. editor / Vladimir N Uversky ; Yuri L Lyubchenko. 1st. ed. UK : Academia Press, 2014. pp. 47-56
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abstract = "Alzheimer s disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment [1]. The primary neuropathologic feature of AD is the presence, in the brain, of amyloid plaques that are formed by aggregation of the ?-amyloid protein (A?) [2]. A?, containing 39 to 42 amino acids, is derived from proteolysis of the amyloid precursor protein (APP) [3]. Much evidence points to A? as the causative factor for the pathogenesis of AD [4?6]. However, the precise mechanism by which A? induces AD-associated neurotoxicity remains elusive. Some in vitro and ex vivo studies show that, rather than the mature A? amyloid fibrils, it is the soluble low- molecular-weight A? oligomers ? which form at the early stage of aggregation ? that cause the neurotoxic effects in AD [7?9]. Alternatively, rather than A? itself, it has been suggested that the process of aggregation induces AD-associated neurotoxicity [10]. On the other hand, interactions with the plasma membrane have been shown to play an important role in the process of A? misfolding and ultimately aggregation [11?16]. Therefore, determination of the three-dimensional structures of A? in different forms (monomers, oligomers, protofibrils and mature fibrils) and characterization of the misfolding and aggregation mechanisms of A? are needed for an understanding of the pathogenesis of AD.........",
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Aguilar, MI, Hou, X, Losic, D, Mechler, AI, Martin, LL & Small, D 2014, Single-molecule imaging of amyloid-beta protein (Abeta) of Alzheimer's disease: from single-molecule structures to aggregation mechanisms and membrane interactions. in VN Uversky & YL Lyubchenko (eds), Bio-nanoimaging Protein Misfolding and Aggregation. 1st edn, Academia Press, UK, pp. 47-56. https://doi.org/10.1016/B978-0-12-394431-3.12001-2

Single-molecule imaging of amyloid-beta protein (Abeta) of Alzheimer's disease: from single-molecule structures to aggregation mechanisms and membrane interactions. / Aguilar, Marie Isabel; Hou, Xu; Losic, Dusan; Mechler, Adam Istvan; Martin, Lisandra Lorraine; Small, David.

Bio-nanoimaging Protein Misfolding and Aggregation. ed. / Vladimir N Uversky; Yuri L Lyubchenko. 1st. ed. UK : Academia Press, 2014. p. 47-56.

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

TY - CHAP

T1 - Single-molecule imaging of amyloid-beta protein (Abeta) of Alzheimer's disease: from single-molecule structures to aggregation mechanisms and membrane interactions

AU - Aguilar, Marie Isabel

AU - Hou, Xu

AU - Losic, Dusan

AU - Mechler, Adam Istvan

AU - Martin, Lisandra Lorraine

AU - Small, David

PY - 2014

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N2 - Alzheimer s disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment [1]. The primary neuropathologic feature of AD is the presence, in the brain, of amyloid plaques that are formed by aggregation of the ?-amyloid protein (A?) [2]. A?, containing 39 to 42 amino acids, is derived from proteolysis of the amyloid precursor protein (APP) [3]. Much evidence points to A? as the causative factor for the pathogenesis of AD [4?6]. However, the precise mechanism by which A? induces AD-associated neurotoxicity remains elusive. Some in vitro and ex vivo studies show that, rather than the mature A? amyloid fibrils, it is the soluble low- molecular-weight A? oligomers ? which form at the early stage of aggregation ? that cause the neurotoxic effects in AD [7?9]. Alternatively, rather than A? itself, it has been suggested that the process of aggregation induces AD-associated neurotoxicity [10]. On the other hand, interactions with the plasma membrane have been shown to play an important role in the process of A? misfolding and ultimately aggregation [11?16]. Therefore, determination of the three-dimensional structures of A? in different forms (monomers, oligomers, protofibrils and mature fibrils) and characterization of the misfolding and aggregation mechanisms of A? are needed for an understanding of the pathogenesis of AD.........

AB - Alzheimer s disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment [1]. The primary neuropathologic feature of AD is the presence, in the brain, of amyloid plaques that are formed by aggregation of the ?-amyloid protein (A?) [2]. A?, containing 39 to 42 amino acids, is derived from proteolysis of the amyloid precursor protein (APP) [3]. Much evidence points to A? as the causative factor for the pathogenesis of AD [4?6]. However, the precise mechanism by which A? induces AD-associated neurotoxicity remains elusive. Some in vitro and ex vivo studies show that, rather than the mature A? amyloid fibrils, it is the soluble low- molecular-weight A? oligomers ? which form at the early stage of aggregation ? that cause the neurotoxic effects in AD [7?9]. Alternatively, rather than A? itself, it has been suggested that the process of aggregation induces AD-associated neurotoxicity [10]. On the other hand, interactions with the plasma membrane have been shown to play an important role in the process of A? misfolding and ultimately aggregation [11?16]. Therefore, determination of the three-dimensional structures of A? in different forms (monomers, oligomers, protofibrils and mature fibrils) and characterization of the misfolding and aggregation mechanisms of A? are needed for an understanding of the pathogenesis of AD.........

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U2 - 10.1016/B978-0-12-394431-3.12001-2

DO - 10.1016/B978-0-12-394431-3.12001-2

M3 - Chapter (Book)

SN - 9780123944313

SP - 47

EP - 56

BT - Bio-nanoimaging Protein Misfolding and Aggregation

A2 - Uversky, Vladimir N

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PB - Academia Press

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Aguilar MI, Hou X, Losic D, Mechler AI, Martin LL, Small D. Single-molecule imaging of amyloid-beta protein (Abeta) of Alzheimer's disease: from single-molecule structures to aggregation mechanisms and membrane interactions. In Uversky VN, Lyubchenko YL, editors, Bio-nanoimaging Protein Misfolding and Aggregation. 1st ed. UK: Academia Press. 2014. p. 47-56 https://doi.org/10.1016/B978-0-12-394431-3.12001-2