Lipids in Amyloid-β processing, aggregation, and toxicity

Morgado, Isabel and Garvey, Megan 2015, Lipids in Amyloid-β processing, aggregation, and toxicity, Advances in experimental medicine and biology, vol. 855, pp. 67-94, doi: 10.1007/978-3-319-17344-3_3.

Title Lipids in Amyloid-β processing, aggregation, and toxicity
Author(s) Morgado, Isabel
Garvey, Megan
Journal name Advances in experimental medicine and biology
Volume number 855
Start page 67
End page 94
Total pages 28
Publisher Springer
Place of publication Berlin, Germany
Publication date 2015
ISSN 0065-2598
Keyword(s) Alzheimer Disease
Amino Acid Sequence
Amyloid beta-Protein Precursor
Apolipoproteins E
Molecular Sequence Data
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Life Sciences & Biomedicine - Other Topics
Research & Experimental Medicine
Amyloid-beta peptide
Alzheimer's disease
Cellular membranes and lipid rafts
Peptide oligomers, protofibrils and fibrils
Apolipoprotein E
Amyloid precursor protein
Summary Aggregation of amyloid-beta (Aβ) peptide is the major event underlying neuronal damage in Alzheimer's disease (AD). Specific lipids and their homeostasis play important roles in this and other neurodegenerative disorders. The complex interplay between the lipids and the generation, clearance or deposition of Aβ has been intensively investigated and is reviewed in this chapter. Membrane lipids can have an important influence on the biogenesis of Aβ from its precursor protein. In particular, increased cholesterol in the plasma membrane augments Aβ generation and shows a strong positive correlation with AD progression. Furthermore, apolipoprotein E, which transports cholesterol in the cerebrospinal fluid and is known to interact with Aβ or compete with it for the lipoprotein receptor binding, significantly influences Aβ clearance in an isoform-specific manner and is the major genetic risk factor for AD. Aβ is an amphiphilic peptide that interacts with various lipids, proteins and their assemblies, which can lead to variation in Aβ aggregation in vitro and in vivo. Upon interaction with the lipid raft components, such as cholesterol, gangliosides and phospholipids, Aβ can aggregate on the cell membrane and thereby disrupt it, perhaps by forming channel-like pores. This leads to perturbed cellular calcium homeostasis, suggesting that Aβ-lipid interactions at the cell membrane probably trigger the neurotoxic cascade in AD. Here, we overview the roles of specific lipids, lipid assemblies and apolipoprotein E in Aβ processing, clearance and aggregation, and discuss the contribution of these factors to the neurotoxicity in AD.
Language eng
DOI 10.1007/978-3-319-17344-3_3
Field of Research 110399 Clinical Sciences not elsewhere classified
11 Medical And Health Sciences
Socio Economic Objective 920502 Health Related to Ageing
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Springer
Persistent URL

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 13 times in TR Web of Science
Scopus Citation Count Cited 13 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 35 Abstract Views  -  Detailed Statistics
Created: Thu, 09 Jun 2016, 10:57:49 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact