Universität zu Köln

Burnouf, Sylvie, Gorsky, Marianna Karina, Dols, Jacqueline, Groenke, Sebastian and Partridge, Linda ORCID: 0000-0001-9615-0094 (2015). A beta(43) is neurotoxic and primes aggregation of A beta(40) in vivo. Acta Neuropathol., 130 (1). S. 35 - 48. NEW YORK: SPRINGER. ISSN 1432-0533

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Abstract

The involvement of Amyloid-beta (A beta) in the pathogenesis of Alzheimer's disease (AD) is well established. However, it is becoming clear that the amyloid load in AD brains consists of a heterogeneous mixture of A beta peptides, implying that a thorough understanding of their respective role and toxicity is crucial for the development of efficient treatments. Besides the well-studied A beta(40) and A beta(42) species, recent data have raised the possibility that A beta(43) peptides might be instrumental in AD pathogenesis, because they are frequently observed in both dense and diffuse amyloid plaques from human AD brains and are highly amyloidogenic in vitro. However, whether A beta(43) is toxic in vivo is currently unclear. Using Drosophila transgenic models of amyloid pathology, we show that A beta(43) peptides are mainly insoluble and highly toxic in vivo, leading to the progressive loss of photoreceptor neurons, altered locomotion and decreased lifespan when expressed in the adult fly nervous system. In addition, we demonstrate that A beta(43) species are able to trigger the aggregation of the typically soluble and non-toxic A beta(40), leading to synergistic toxic effects on fly lifespan and climbing ability, further suggesting that A beta(43) peptides could act as a nucleating factor in AD brains. Altogether, our study demonstrates high pathogenicity of A beta(43) species in vivo and supports the idea that A beta(43) contributes to the pathological events leading to neurodegeneration in AD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Burnouf, Sylvie UNSPECIFIED UNSPECIFIED UNSPECIFIED Gorsky, Marianna Karina UNSPECIFIED UNSPECIFIED UNSPECIFIED Dols, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Groenke, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-399993
DOI:	10.1007/s00401-015-1419-y
Journal or Publication Title:	Acta Neuropathol.
Volume:	130
Number:	1
Page Range:	S. 35 - 48
Date:	2015
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0533
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALZHEIMERS-DISEASE; A-BETA; PINK1 LOSS; DROSOPHILA; A-BETA-42; BRAIN; MODEL; NEURODEGENERATION; PROTEIN; DEGENERATION Multiple languages Clinical Neurology; Neurosciences; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39999