N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits

N -truncated Aβ 4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ 4-42 rapidly forms aggregates possessing a high aggregatio...

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Veröffentlicht in:Acta neuropathologica 2013-08, Vol.126 (2), p.189-205
Hauptverfasser: Bouter, Yvonne, Dietrich, Katharina, Wittnam, Jessica L., Rezaei-Ghaleh, Nasrollah, Pillot, Thierry, Papot-Couturier, Sophie, Lefebvre, Thomas, Sprenger, Frederick, Wirths, Oliver, Zweckstetter, Markus, Bayer, Thomas A.
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container_issue 2
container_start_page 189
container_title Acta neuropathologica
container_volume 126
creator Bouter, Yvonne
Dietrich, Katharina
Wittnam, Jessica L.
Rezaei-Ghaleh, Nasrollah
Pillot, Thierry
Papot-Couturier, Sophie
Lefebvre, Thomas
Sprenger, Frederick
Wirths, Oliver
Zweckstetter, Markus
Bayer, Thomas A.
description N -truncated Aβ 4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ 4-42 rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ 4-42 is as toxic as pyroglutamate Aβ 3-42 and Aβ 1-42 . In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ 4-42 , pyroglutamate Aβ 3-42 and Aβ 1-42 . Transgenic mice expressing Aβ 4-42 (Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ 4-42 correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that N -truncated Aβ 4-42 triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction.
doi_str_mv 10.1007/s00401-013-1129-2
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subjects Alzheimer Disease - etiology
Alzheimer Disease - pathology
Alzheimer's disease
Amyloid - chemistry
Amyloid - ultrastructure
Amyloid beta-Peptides - chemistry
Amyloid beta-Peptides - genetics
Amyloid beta-Peptides - toxicity
Amyloid beta-protein
Animals
Behavior, Animal - physiology
Brain
Female
Fetus - cytology
Genetic engineering
Humans
Injections, Intraventricular
Male
Maze Learning - physiology
Medicine
Medicine & Public Health
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Electron, Transmission
Molecular Weight
Nerve Degeneration - etiology
Nerve Degeneration - pathology
Neurons - cytology
Neurons - drug effects
Neurons - pathology
Neurosciences
Original Paper
Pathology
Peptides
Pregnancy
Primary Cell Culture
Rats
Rats, Wistar
Solubility
Space Perception - physiology
title N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits
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