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Parenchymal and vascular Aβ-deposition and its effects on the degeneration of neurons and cognition in Alzheimer's disease
- The deposition of the amyloid β-protein (Aβ) is one of the pathological hallmarks of Alzheimer's disease (AD). Aβ-deposits show the morphology of senile plaques and cerebral amyloid angiopathy (CAA). Senile plaques and vascular Aβ-deposits occur first in neocorti-cal areas. Then, they expand hierarchically into further brain regions. The distribution of Aβ plaques throughout the entire brain, thereby correlates with the clinical status of the patients. Imaging techniques for Aβ make use of the hierarchical distribution of Aβ to distinguish AD patients from non-AD patients. However, pathology seen in AD patients represents a late stage of a pathological process starting 10–30 years earlier in cognitively normal individuals. In addition to the fibrillar amyloid of senile plaques, oligomeric and monomeric Aβ is found in the brain. Recent studies revealed that oligomeric Aβ is presumably the most toxic Aβ-aggregate, which interacts with glutamatergic synapses. In doing so, dendrites are presumed to be the primary target for Aβ-toxicity. In addition, vascular Aβ-deposits can lead to capillary occlusion and blood flow disturbances presumably contributing to the alteration of neurons in addition to the direct neurotoxic effects of Aβ. All these findings point to an important role of Aβ and its aggregates in the neurodegenerative process of AD. Since there is already significant neuron loss in AD patients, treatment strategies aimed at reducing the amyloid load will presumably not cure the symptoms of dementia but they may stop disease progression. Therefore, it seems to be necessary to protect the brain from Aβ-toxicity already in stages of the disease with minor neuron loss before the onset of cognitive symptoms.
Author: | Dietmar Rudolf Thal, W. Sue T. Griffin, Heiko Braak |
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URN: | urn:nbn:de:hebis:30:3-279579 |
DOI: | https://doi.org/10.1111/j.1582-4934.2008.00411.x |
ISSN: | 1582-4934 |
ISSN: | 1582-1838 |
Parent Title (English): | Journal of cellular and molecular medicine |
Publisher: | Wiley-Blackwell |
Place of publication: | Oxford |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2008/07/10 |
Date of first Publication: | 2008/07/10 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2013/02/08 |
Tag: | Alzheimer; amyloid plaques; amyloid β-protein; cerebral amyloid angiopathy; dendritic degeneration |
Volume: | 12 |
Issue: | 5b |
Page Number: | 15 |
First Page: | 1848 |
Last Page: | 1862 |
Note: | © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
HeBIS-PPN: | 327963034 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Licence (German): | ![]() |