Association of AEBP1 and NRN1 RNA expression with Alzheimer's disease and neurofibrillary tangle density in middle temporal gyrus

Ignazio S. Piras, Jonida Krate, Elaine Delvaux, Jennifer Nolz, Matthew D. De Both, Diego Mastroeni, Geidy E. Serrano, Lucia I. Sue, Thomas G. Beach, Paul Coleman, Matthew J. Huentelman

Research output: Contribution to journalArticle

Abstract

We explored RNA expression changes in the middle temporal gyrus (MTG) of Alzheimer's Disease patients (AD) by RNA sequencing the whole transcriptome of 8 AD and 8 Non-Demented (ND) controls. We used three additional expression datasets from related brain regions to validate the findings. The results highlighted the upregulation of AEBP1 and downregulation of NRN1 in AD, as well as their association with Braak staging and neurofibrillary tangles density. Furthermore, more than 400 protein-coding RNAs enriched for “Clathrin-mediated endocytosis” were validated in independent datasets from the same brain region. Finally, using in silico prediction analysis we found a signature of 52 non-protein coding RNAs that perturb key pathways involved in GABAergic transmission and peptide chain elongation. The association of AEBP1 in our data confirmed other published work examining gene expression in the hippocampus of AD patients. NRN1 is involved in neurite outgrowth, and in previous studies it has been shown to reverse synaptic defects and cognitive function impairment in Tg2576 mice. Finally, our results on non-protein coding RNAs suggest a role of these transcripts in altering synaptic and amyloid-β associated pathways.

Original languageEnglish (US)
Pages (from-to)217-224
Number of pages8
JournalBrain Research
Volume1719
DOIs
StatePublished - Sep 15 2019

Fingerprint

Neurofibrillary Tangles
Temporal Lobe
Alzheimer Disease
RNA
Untranslated RNA
RNA Sequence Analysis
Clathrin
Brain
Endocytosis
Transcriptome
Amyloid
Computer Simulation
Cognition
Hippocampus
Up-Regulation
Down-Regulation
Gene Expression
Peptides
Proteins

Keywords

  • AEBP1
  • Alzheimer's disease
  • Braak staging
  • Neurofibrillary tangles
  • Non-protein coding RNAs
  • RNA sequencing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Association of AEBP1 and NRN1 RNA expression with Alzheimer's disease and neurofibrillary tangle density in middle temporal gyrus. / Piras, Ignazio S.; Krate, Jonida; Delvaux, Elaine; Nolz, Jennifer; De Both, Matthew D.; Mastroeni, Diego; Serrano, Geidy E.; Sue, Lucia I.; Beach, Thomas G.; Coleman, Paul; Huentelman, Matthew J.

In: Brain Research, Vol. 1719, 15.09.2019, p. 217-224.

Research output: Contribution to journalArticle

Piras, Ignazio S. ; Krate, Jonida ; Delvaux, Elaine ; Nolz, Jennifer ; De Both, Matthew D. ; Mastroeni, Diego ; Serrano, Geidy E. ; Sue, Lucia I. ; Beach, Thomas G. ; Coleman, Paul ; Huentelman, Matthew J. / Association of AEBP1 and NRN1 RNA expression with Alzheimer's disease and neurofibrillary tangle density in middle temporal gyrus. In: Brain Research. 2019 ; Vol. 1719. pp. 217-224.
@article{d83fc4abf70747b9b4da1f3cde1db269,
title = "Association of AEBP1 and NRN1 RNA expression with Alzheimer's disease and neurofibrillary tangle density in middle temporal gyrus",
abstract = "We explored RNA expression changes in the middle temporal gyrus (MTG) of Alzheimer's Disease patients (AD) by RNA sequencing the whole transcriptome of 8 AD and 8 Non-Demented (ND) controls. We used three additional expression datasets from related brain regions to validate the findings. The results highlighted the upregulation of AEBP1 and downregulation of NRN1 in AD, as well as their association with Braak staging and neurofibrillary tangles density. Furthermore, more than 400 protein-coding RNAs enriched for “Clathrin-mediated endocytosis” were validated in independent datasets from the same brain region. Finally, using in silico prediction analysis we found a signature of 52 non-protein coding RNAs that perturb key pathways involved in GABAergic transmission and peptide chain elongation. The association of AEBP1 in our data confirmed other published work examining gene expression in the hippocampus of AD patients. NRN1 is involved in neurite outgrowth, and in previous studies it has been shown to reverse synaptic defects and cognitive function impairment in Tg2576 mice. Finally, our results on non-protein coding RNAs suggest a role of these transcripts in altering synaptic and amyloid-β associated pathways.",
keywords = "AEBP1, Alzheimer's disease, Braak staging, Neurofibrillary tangles, Non-protein coding RNAs, RNA sequencing",
author = "Piras, {Ignazio S.} and Jonida Krate and Elaine Delvaux and Jennifer Nolz and {De Both}, {Matthew D.} and Diego Mastroeni and Serrano, {Geidy E.} and Sue, {Lucia I.} and Beach, {Thomas G.} and Paul Coleman and Huentelman, {Matthew J.}",
year = "2019",
month = "9",
day = "15",
doi = "10.1016/j.brainres.2019.06.004",
language = "English (US)",
volume = "1719",
pages = "217--224",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - Association of AEBP1 and NRN1 RNA expression with Alzheimer's disease and neurofibrillary tangle density in middle temporal gyrus

AU - Piras, Ignazio S.

AU - Krate, Jonida

AU - Delvaux, Elaine

AU - Nolz, Jennifer

AU - De Both, Matthew D.

AU - Mastroeni, Diego

AU - Serrano, Geidy E.

AU - Sue, Lucia I.

AU - Beach, Thomas G.

AU - Coleman, Paul

AU - Huentelman, Matthew J.

PY - 2019/9/15

Y1 - 2019/9/15

N2 - We explored RNA expression changes in the middle temporal gyrus (MTG) of Alzheimer's Disease patients (AD) by RNA sequencing the whole transcriptome of 8 AD and 8 Non-Demented (ND) controls. We used three additional expression datasets from related brain regions to validate the findings. The results highlighted the upregulation of AEBP1 and downregulation of NRN1 in AD, as well as their association with Braak staging and neurofibrillary tangles density. Furthermore, more than 400 protein-coding RNAs enriched for “Clathrin-mediated endocytosis” were validated in independent datasets from the same brain region. Finally, using in silico prediction analysis we found a signature of 52 non-protein coding RNAs that perturb key pathways involved in GABAergic transmission and peptide chain elongation. The association of AEBP1 in our data confirmed other published work examining gene expression in the hippocampus of AD patients. NRN1 is involved in neurite outgrowth, and in previous studies it has been shown to reverse synaptic defects and cognitive function impairment in Tg2576 mice. Finally, our results on non-protein coding RNAs suggest a role of these transcripts in altering synaptic and amyloid-β associated pathways.

AB - We explored RNA expression changes in the middle temporal gyrus (MTG) of Alzheimer's Disease patients (AD) by RNA sequencing the whole transcriptome of 8 AD and 8 Non-Demented (ND) controls. We used three additional expression datasets from related brain regions to validate the findings. The results highlighted the upregulation of AEBP1 and downregulation of NRN1 in AD, as well as their association with Braak staging and neurofibrillary tangles density. Furthermore, more than 400 protein-coding RNAs enriched for “Clathrin-mediated endocytosis” were validated in independent datasets from the same brain region. Finally, using in silico prediction analysis we found a signature of 52 non-protein coding RNAs that perturb key pathways involved in GABAergic transmission and peptide chain elongation. The association of AEBP1 in our data confirmed other published work examining gene expression in the hippocampus of AD patients. NRN1 is involved in neurite outgrowth, and in previous studies it has been shown to reverse synaptic defects and cognitive function impairment in Tg2576 mice. Finally, our results on non-protein coding RNAs suggest a role of these transcripts in altering synaptic and amyloid-β associated pathways.

KW - AEBP1

KW - Alzheimer's disease

KW - Braak staging

KW - Neurofibrillary tangles

KW - Non-protein coding RNAs

KW - RNA sequencing

UR - http://www.scopus.com/inward/record.url?scp=85066929013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066929013&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2019.06.004

DO - 10.1016/j.brainres.2019.06.004

M3 - Article

C2 - 31176712

AN - SCOPUS:85066929013

VL - 1719

SP - 217

EP - 224

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -