Intracellular Abeta and cognitive deficits precede beta-amyloid deposition in transgenic arcAbeta mice.

Details

Serval ID
serval:BIB_3CDB82048EC5
Type
Article: article from journal or magazin.
Collection
Publications
Title
Intracellular Abeta and cognitive deficits precede beta-amyloid deposition in transgenic arcAbeta mice.
Journal
Neurobiology of aging
Author(s)
Knobloch M., Konietzko U., Krebs D.C., Nitsch R.M.
ISSN
1558-1497 (Electronic)
ISSN-L
0197-4580
Publication state
Published
Issued date
09/2007
Peer-reviewed
Oui
Volume
28
Number
9
Pages
1297-1306
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The brain pathology of Alzheimer's disease is characterized by abnormally aggregated Abeta in extracellular beta-amyloid plaques and along blood vessel walls, but the relation to intracellular Abeta remains unclear. To address the role of intracellular Abeta deposition in vivo, we expressed human APP with the combined Swedish and Arctic mutations in mice (arcAbeta mice). Intracellular punctate deposits of Abeta occurred concomitantly with robust cognitive impairments at the age of 6 months before the onset of beta-amyloid plaque formation and cerebral beta-amyloid angiopathy. beta-Amyloid plaques from arcAbeta mice had distinct dense-core morphologies with blood vessels appearing as seeding origins, suggesting reduced clearance of Abeta across blood vessels in arcAbeta mice. The co-incidence of intracellular Abeta deposits with behavioral deficits support an early role of intracellular Abeta in the pathophysiological cascade leading to beta-amyloid formation and functional impairment.
Keywords
Age Factors, Amyloid beta-Peptides/metabolism, Amyloid beta-Protein Precursor/genetics, Analysis of Variance, Animals, Avoidance Learning/physiology, Behavior, Animal/physiology, Cognition Disorders/genetics, Exploratory Behavior/physiology, Humans, Maze Learning/physiology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity/genetics, Mutation/physiology, Neurologic Examination, Plaque, Amyloid/metabolism, Plaque, Amyloid/pathology, Rotarod Performance Test/methods, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
Pubmed
Web of science
Create date
25/05/2018 8:48
Last modification date
20/08/2019 13:33
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