Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology

Abstract Tau pathology in Alzheimer’s disease (AD) spreads in a predictable pattern that corresponds with disease symptoms and severity. At post-mortem there are cortical regions that range from mildly to severely affected by tau pathology and neuronal loss. A comparison of the molecular signatures...

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Autores principales:	Boris Guennewig, Julia Lim, Lee Marshall, Andrew N. McCorkindale, Patrick J. Paasila, Ellis Patrick, Jillian J. Kril, Glenda M. Halliday, Antony A. Cooper, Greg T. Sutherland
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d30c932bbdf4fafba8d0669bc8e6e7e
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spelling	oai:doaj.org-article:3d30c932bbdf4fafba8d0669bc8e6e7e2021-12-02T15:53:58ZDefining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology10.1038/s41598-021-83872-z2045-2322https://doaj.org/article/3d30c932bbdf4fafba8d0669bc8e6e7e2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83872-zhttps://doaj.org/toc/2045-2322Abstract Tau pathology in Alzheimer’s disease (AD) spreads in a predictable pattern that corresponds with disease symptoms and severity. At post-mortem there are cortical regions that range from mildly to severely affected by tau pathology and neuronal loss. A comparison of the molecular signatures of these differentially affected areas within cases and between cases and controls may allow the temporal modelling of disease progression. Here we used RNA sequencing to explore differential gene expression in the mildly affected primary visual cortex and moderately affected precuneus of ten age-, gender- and RNA quality-matched post-mortem brains from AD patients and healthy controls. The two regions in AD cases had similar transcriptomic signatures but there were broader abnormalities in the precuneus consistent with the greater tau load. Both regions were characterised by upregulation of immune-related genes such as those encoding triggering receptor expressed on myeloid cells 2 and membrane spanning 4-domains A6A and milder changes in insulin/IGF1 signalling. The precuneus in AD was also characterised by changes in vesicle secretion and downregulation of the interneuronal subtype marker, somatostatin. The ‘early’ AD transcriptome is characterised by perturbations in synaptic vesicle secretion on a background of neuroimmune dysfunction. In particular, the synaptic deficits that characterise AD may begin with the somatostatin division of inhibitory neurotransmission.Boris GuennewigJulia LimLee MarshallAndrew N. McCorkindalePatrick J. PaasilaEllis PatrickJillian J. KrilGlenda M. HallidayAntony A. CooperGreg T. SutherlandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Boris Guennewig Julia Lim Lee Marshall Andrew N. McCorkindale Patrick J. Paasila Ellis Patrick Jillian J. Kril Glenda M. Halliday Antony A. Cooper Greg T. Sutherland Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology
description	Abstract Tau pathology in Alzheimer’s disease (AD) spreads in a predictable pattern that corresponds with disease symptoms and severity. At post-mortem there are cortical regions that range from mildly to severely affected by tau pathology and neuronal loss. A comparison of the molecular signatures of these differentially affected areas within cases and between cases and controls may allow the temporal modelling of disease progression. Here we used RNA sequencing to explore differential gene expression in the mildly affected primary visual cortex and moderately affected precuneus of ten age-, gender- and RNA quality-matched post-mortem brains from AD patients and healthy controls. The two regions in AD cases had similar transcriptomic signatures but there were broader abnormalities in the precuneus consistent with the greater tau load. Both regions were characterised by upregulation of immune-related genes such as those encoding triggering receptor expressed on myeloid cells 2 and membrane spanning 4-domains A6A and milder changes in insulin/IGF1 signalling. The precuneus in AD was also characterised by changes in vesicle secretion and downregulation of the interneuronal subtype marker, somatostatin. The ‘early’ AD transcriptome is characterised by perturbations in synaptic vesicle secretion on a background of neuroimmune dysfunction. In particular, the synaptic deficits that characterise AD may begin with the somatostatin division of inhibitory neurotransmission.
format	article
author	Boris Guennewig Julia Lim Lee Marshall Andrew N. McCorkindale Patrick J. Paasila Ellis Patrick Jillian J. Kril Glenda M. Halliday Antony A. Cooper Greg T. Sutherland
author_facet	Boris Guennewig Julia Lim Lee Marshall Andrew N. McCorkindale Patrick J. Paasila Ellis Patrick Jillian J. Kril Glenda M. Halliday Antony A. Cooper Greg T. Sutherland
author_sort	Boris Guennewig
title	Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology
title_short	Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology
title_full	Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology
title_fullStr	Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology
title_full_unstemmed	Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology
title_sort	defining early changes in alzheimer’s disease from rna sequencing of brain regions differentially affected by pathology
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3d30c932bbdf4fafba8d0669bc8e6e7e
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Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology

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