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A highly insoluble ...
A highly insoluble state of Abeta similar to that of Alzheimer's disease brain is found in Arctic APP transgenic mice.
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- Philipson, Ola (author)
- Uppsala universitet,Geriatrik,Uppsala University
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- Hammarström, Per (author)
- Linköpings universitet,Biokemi,Tekniska högskolan
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- Nilsson, Peter (author)
- Linköpings universitet,Organisk Kemi,Tekniska högskolan
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- Portelius, Erik, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska University Hospital
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- Olofsson, Tommie (author)
- Uppsala universitet,Institutionen för genetik och patologi,Uppsala University
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- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik,Uppsala University
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- Hyman, Bradley T (author)
- Massachusetts General Hospital
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska University Hospital
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- Lannfelt, Lars (author)
- Uppsala universitet,Geriatrik,Uppsala University
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- Kalimo, Hannu (author)
- Uppsala universitet,Institutionen för genetik och patologi,Uppsala University
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- Nilsson, Lars N G (author)
- Uppsala universitet,Geriatrik
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(creator_code:org_t)
- Elsevier BV, 2009
- 2009
- English.
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In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:9, s. 1393-405
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Keyword
- 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
- Immunotherapy
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Philipson, Ola
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Hammarström, Per
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Nilsson, Peter
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Portelius, Erik, ...
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Olofsson, Tommie
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Ingelsson, Marti ...
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show more...
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Hyman, Bradley T
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Blennow, Kaj, 19 ...
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Lannfelt, Lars
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Kalimo, Hannu
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Nilsson, Lars N ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
- Articles in the publication
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Neurobiology of ...
- By the university
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University of Gothenburg
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Uppsala University
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Linköping University