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A highly insoluble state … - University of Gothenburg, Sweden Till startsida
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A highly insoluble state of Abeta similar to that of Alzheimer's disease brain is found in Arctic APP transgenic mice.

Journal article
Authors Ola Philipson
Per Hammarström
K Peter R Nilsson
Erik Portelius
Tommie Olofsson
Martin Ingelsson
Bradley T Hyman
Kaj Blennow
Lars Lannfelt
Hannu Kalimo
Lars N G Nilsson
Published in Neurobiology of aging
Volume 30
Issue 9
Pages 1393-405
ISSN 1558-1497
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 1393-405
Language en
Keywords Aged, Aged, 80 and over, Alzheimer Disease, genetics, metabolism, physiopathology, Amyloid beta-Protein, antagonists & inhibitors, chemistry, metabolism, Amyloid beta-Protein Precursor, genetics, Animals, Antibodies, pharmacology, therapeutic use, Brain, metabolism, pathology, physiopathology, Disease Models, Animal, Genetic Predisposition to Disease, genetics, Humans, Mice, Mice, Transgenic, Microscopy, Electron, Transmission, Mutation, genetics, Senile Plaques, genetics, metabolism, pathology, Solubility
Subject categories Psychiatry


Amyloid-beta (Abeta) is a major drug target in Alzheimer's disease. Here, we demonstrate that deposited Abeta is SDS insoluble in tgAPP-ArcSwe, a transgenic mouse model harboring the Arctic (E693G) and Swedish (KM670/671NL) APP mutations. Formic acid was needed to extract the majority of deposited Abeta in both tgAPP-ArcSwe and Alzheimer's disease brain, but not in a commonly used type of mouse model with the Swedish mutation alone. Interestingly, the insoluble state of Arctic Abeta was determined early on and did not gradually evolve with time. In tgAPP-ArcSwe, Abeta plaques displayed a patchy morphology with bundles of Abeta fibrils, whereas amyloid cores in tgAPP-Swe were circular with radiating fibrils. Amyloid was more densely stacked in tgAPP-ArcSwe, as demonstrated with a conformation sensitive probe. A reduced increase in plasma Abeta was observed following acute administration of an Abeta antibody in tgAPP-ArcSwe, results that might imply reduced brain to plasma Abeta efflux. TgAPP-ArcSwe, with its insoluble state of deposited Abeta, could serve as a complementary model to better predict the outcome of clinical trials.

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