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Licensed Unlicensed Requires Authentication Published by De Gruyter February 15, 2018

Amyloid toxicity in Alzheimer’s disease

Allison B. Reiss, Hirra A. Arain, Mark M. Stecker, Nicolle M. Siegart and Lora J. Kasselman

Abstract

A major feature of Alzheimer’s disease (AD) pathology is the plaque composed of aggregated amyloid-β (Aβ) peptide. Although these plaques may have harmful properties, there is much evidence to implicate soluble oligomeric Aβ as the primary noxious form. Aβ oligomers can be generated both extracellularly and intracellularly. Aβ is toxic to neurons in a myriad of ways. It can cause pore formation resulting in the leakage of ions, disruption of cellular calcium balance, and loss of membrane potential. It can promote apoptosis, cause synaptic loss, and disrupt the cytoskeleton. Current treatments for AD are limited and palliative. Much research and effort is being devoted to reducing Aβ production as an approach to slowing or preventing the development of AD. Aβ formation results from the amyloidogenic cleavage of human amyloid precursor protein (APP). Reconfiguring this process to disfavor amyloid generation might be possible through the reduction of APP or inhibition of enzymes that convert the precursor protein to amyloid.

Acknowledgments

This work was supported by the Herb and Evelyn Abrams Family Amyloid Research Fund, the Alzheimer’s Foundation of America, the Alzheimer’s Disease Resource Center, and the Elizabeth Daniell Research Fund.

  1. Conflict of interest statement: The authors declare that they have no conflict of interests.

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Received: 2017-08-08
Accepted: 2017-12-17
Published Online: 2018-02-15
Published in Print: 2018-08-28

©2018 Walter de Gruyter GmbH, Berlin/Boston

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