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Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease

One unexplained feature of Alzheimer’s disease (AD) is that the lateral entorhinal cortex undergoes neurodegeneration before other brain areas. However, this brain region does not have elevated levels of amyloid peptides in comparison with undamaged regions. What is the cause of this special vulnera...

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Autor principal: Young, John K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592839/
https://www.ncbi.nlm.nih.gov/pubmed/33163897
http://dx.doi.org/10.3233/ADR-200218
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author Young, John K.
author_facet Young, John K.
author_sort Young, John K.
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description One unexplained feature of Alzheimer’s disease (AD) is that the lateral entorhinal cortex undergoes neurodegeneration before other brain areas. However, this brain region does not have elevated levels of amyloid peptides in comparison with undamaged regions. What is the cause of this special vulnerability of the entorhinal cortex? One special feature of the lateral entorhinal cortex is that it projects to newborn neurons that have undergone adult neurogenesis in the dentate gyrus of the hippocampus. Neurogenesis is abnormal in human AD brains, and modulation of neurogenesis in experimental animals influences the course of AD. This complex process of neurogenesis may expose axon terminals originating from neurons of the entorhinal cortex to a unique combination of molecules that can enhance toxic effects of amyloid. Retrograde degeneration of neurons with axons terminating in the dentate gyrus provides a likely explanation for the spatial patterns of neuronal cell death seen in AD. Specialized astrocytes in the dentate gyrus participate in adult neurogenesis and produce fatty acid binding protein7 (FABP7). These FABP7+ cells undergo an aging-related mitochondrial pathology that likely impairs their functions. This age-related abnormality may contribute to the impairment in neurogenesis seen in aging and Alzheimer’s disease. Also, a compromised function of these astrocytes likely results in local elevations of palmitic acid, iron, copper, and glucose, which all enhance the toxicity of amyloid peptides. Treatments that modulate neurogenesis or diminish the production of these toxic substances may prove more successful than treatments that are solely aimed at reducing the amyloid burden alone.
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spelling pubmed-75928392020-11-05 Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease Young, John K. J Alzheimers Dis Rep Hypothesis One unexplained feature of Alzheimer’s disease (AD) is that the lateral entorhinal cortex undergoes neurodegeneration before other brain areas. However, this brain region does not have elevated levels of amyloid peptides in comparison with undamaged regions. What is the cause of this special vulnerability of the entorhinal cortex? One special feature of the lateral entorhinal cortex is that it projects to newborn neurons that have undergone adult neurogenesis in the dentate gyrus of the hippocampus. Neurogenesis is abnormal in human AD brains, and modulation of neurogenesis in experimental animals influences the course of AD. This complex process of neurogenesis may expose axon terminals originating from neurons of the entorhinal cortex to a unique combination of molecules that can enhance toxic effects of amyloid. Retrograde degeneration of neurons with axons terminating in the dentate gyrus provides a likely explanation for the spatial patterns of neuronal cell death seen in AD. Specialized astrocytes in the dentate gyrus participate in adult neurogenesis and produce fatty acid binding protein7 (FABP7). These FABP7+ cells undergo an aging-related mitochondrial pathology that likely impairs their functions. This age-related abnormality may contribute to the impairment in neurogenesis seen in aging and Alzheimer’s disease. Also, a compromised function of these astrocytes likely results in local elevations of palmitic acid, iron, copper, and glucose, which all enhance the toxicity of amyloid peptides. Treatments that modulate neurogenesis or diminish the production of these toxic substances may prove more successful than treatments that are solely aimed at reducing the amyloid burden alone. IOS Press 2020-09-03 /pmc/articles/PMC7592839/ /pubmed/33163897 http://dx.doi.org/10.3233/ADR-200218 Text en © 2020 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Hypothesis
Young, John K.
Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease
title Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease
title_full Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease
title_fullStr Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease
title_full_unstemmed Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease
title_short Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease
title_sort neurogenesis makes a crucial contribution to the neuropathology of alzheimer’s disease
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592839/
https://www.ncbi.nlm.nih.gov/pubmed/33163897
http://dx.doi.org/10.3233/ADR-200218
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