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Nerve Growth Factor Compromise in Down Syndrome

The basal forebrain cholinergic system relies on trophic support by nerve growth factor (NGF) to maintain its phenotype and function. In Alzheimer’s disease (AD), basal forebrain cholinergic neurons (BFCNs) undergo progressive atrophy, suggesting a deficit in NGF trophic support. Within the central...

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Autores principales: Do Carmo, Sonia, Kannel, Benjamin, Cuello, A. Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381049/
https://www.ncbi.nlm.nih.gov/pubmed/34434101
http://dx.doi.org/10.3389/fnagi.2021.719507
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author Do Carmo, Sonia
Kannel, Benjamin
Cuello, A. Claudio
author_facet Do Carmo, Sonia
Kannel, Benjamin
Cuello, A. Claudio
author_sort Do Carmo, Sonia
collection PubMed
description The basal forebrain cholinergic system relies on trophic support by nerve growth factor (NGF) to maintain its phenotype and function. In Alzheimer’s disease (AD), basal forebrain cholinergic neurons (BFCNs) undergo progressive atrophy, suggesting a deficit in NGF trophic support. Within the central nervous system, NGF maturation and degradation are tightly regulated by an activity-dependent metabolic cascade. Here, we present a brief overview of the characteristics of Alzheimer’s pathology in Down syndrome (DS) with an emphasis on this NGF metabolic pathway’s disruption during the evolving Alzheimer’s pathology. Such NGF dysmetabolism is well-established in Alzheimer’s brains with advanced pathology and has been observed in mild cognitive impairment (MCI) and non-demented individuals with elevated brain amyloid levels. As individuals with DS inexorably develop AD, we then review findings that support the existence of a similar NGF dysmetabolism in DS coinciding with atrophy of the basal forebrain cholinergic system. Lastly, we discuss the potential of NGF-related biomarkers as indicators of an evolving Alzheimer’s pathology in DS.
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spelling pubmed-83810492021-08-24 Nerve Growth Factor Compromise in Down Syndrome Do Carmo, Sonia Kannel, Benjamin Cuello, A. Claudio Front Aging Neurosci Neuroscience The basal forebrain cholinergic system relies on trophic support by nerve growth factor (NGF) to maintain its phenotype and function. In Alzheimer’s disease (AD), basal forebrain cholinergic neurons (BFCNs) undergo progressive atrophy, suggesting a deficit in NGF trophic support. Within the central nervous system, NGF maturation and degradation are tightly regulated by an activity-dependent metabolic cascade. Here, we present a brief overview of the characteristics of Alzheimer’s pathology in Down syndrome (DS) with an emphasis on this NGF metabolic pathway’s disruption during the evolving Alzheimer’s pathology. Such NGF dysmetabolism is well-established in Alzheimer’s brains with advanced pathology and has been observed in mild cognitive impairment (MCI) and non-demented individuals with elevated brain amyloid levels. As individuals with DS inexorably develop AD, we then review findings that support the existence of a similar NGF dysmetabolism in DS coinciding with atrophy of the basal forebrain cholinergic system. Lastly, we discuss the potential of NGF-related biomarkers as indicators of an evolving Alzheimer’s pathology in DS. Frontiers Media S.A. 2021-08-09 /pmc/articles/PMC8381049/ /pubmed/34434101 http://dx.doi.org/10.3389/fnagi.2021.719507 Text en Copyright © 2021 Do Carmo, Kannel and Cuello. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Do Carmo, Sonia
Kannel, Benjamin
Cuello, A. Claudio
Nerve Growth Factor Compromise in Down Syndrome
title Nerve Growth Factor Compromise in Down Syndrome
title_full Nerve Growth Factor Compromise in Down Syndrome
title_fullStr Nerve Growth Factor Compromise in Down Syndrome
title_full_unstemmed Nerve Growth Factor Compromise in Down Syndrome
title_short Nerve Growth Factor Compromise in Down Syndrome
title_sort nerve growth factor compromise in down syndrome
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381049/
https://www.ncbi.nlm.nih.gov/pubmed/34434101
http://dx.doi.org/10.3389/fnagi.2021.719507
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