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Open Access 01-06-2018 | Review

Somatic mutations in neurons during aging and neurodegeneration

Authors: Bert M. Verheijen, Marc Vermulst, Fred W. van Leeuwen

Published in: Acta Neuropathologica | Issue 6/2018

Abstract

The nervous system is composed of a large variety of neurons with a diverse array of morphological and functional properties. This heterogeneity is essential for the construction and maintenance of a distinct set of neural networks with unique characteristics. Accumulating evidence now indicates that neurons do not only differ at a functional level, but also at the genomic level. These genomic discrepancies seem to be the result of somatic mutations that emerge in nervous tissue during development and aging. Ultimately, these mutations bring about a genetically heterogeneous population of neurons, a phenomenon that is commonly referred to as “somatic brain mosaicism”. Improved understanding of the development and consequences of somatic brain mosaicism is crucial to understand the impact of somatic mutations on neuronal function in human aging and disease. Here, we highlight a number of topics related to somatic brain mosaicism, including some early experimental evidence for somatic mutations in post-mitotic neurons of the hypothalamo-neurohypophyseal system. We propose that age-related somatic mutations are particularly interesting, because aging is a major risk factor for a variety of neuronal diseases, including Alzheimer’s disease. We highlight potential links between somatic mutations and the development of these diseases and argue that recent advances in single-cell genomics and in vivo physiology have now finally made it possible to dissect the origins and consequences of neuronal mutations in unprecedented detail.

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Title: Somatic mutations in neurons during aging and neurodegeneration
Authors: Bert M. Verheijen
Marc Vermulst
Fred W. van Leeuwen
Publication date: 01-06-2018
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 6/2018
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-018-1850-y

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Somatic mutations in neurons during aging and neurodegeneration

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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