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


Knobloch, M; Konietzko, U; Krebs, D C; Nitsch, R M (2007). Intracellular Abeta and cognitive deficits precede beta-amyloid deposition in transgenic arcAbeta mice. Neurobiology of Aging, 28(9):1297-1306.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2007
Deposited On:06 Sep 2011 08:37
Last Modified:16 Aug 2016 10:14
Publisher:Elsevier
ISSN:0197-4580
Publisher DOI:https://doi.org/10.1016/j.neurobiolaging.2006.06.019
PubMed ID:16876915

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