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Transcriptomics Profiling of Alzheimer's Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs.

Publication ,  Journal Article
Magistri, M; Velmeshev, D; Makhmutova, M; Faghihi, MA
Published in: J Alzheimers Dis
2015

The underlying genetic variations of late-onset Alzheimer's disease (LOAD) cases remain largely unknown. A combination of genetic variations with variable penetrance and lifetime epigenetic factors may converge on transcriptomic alterations that drive LOAD pathological process. Transcriptome profiling using deep sequencing technology offers insight into common altered pathways regardless of underpinning genetic or epigenetic factors and thus represents an ideal tool to investigate molecular mechanisms related to the pathophysiology of LOAD. We performed directional RNA sequencing on high quality RNA samples extracted from hippocampi of LOAD and age-matched controls. We further validated our data using qRT-PCR on a larger set of postmortem brain tissues, confirming downregulation of the gene encoding substance P (TAC1) and upregulation of the gene encoding the plasminogen activator inhibitor-1 (SERPINE1). Pathway analysis indicates dysregulation in neural communication, cerebral vasculature, and amyloid-β clearance. Beside protein coding genes, we identified several annotated and non-annotated long noncoding RNAs that are differentially expressed in LOAD brain tissues, three of them are activity-dependent regulated and one is induced by Aβ(1-42) exposure of human neural cells. Our data provide a comprehensive list of transcriptomics alterations in LOAD hippocampi and warrant holistic approach including both coding and non-coding RNAs in functional studies aimed to understand the pathophysiology of LOAD.

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Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2015

Volume

48

Issue

3

Start / End Page

647 / 665

Location

Netherlands

Related Subject Headings

  • Transcriptome
  • Sequence Analysis, RNA
  • Real-Time Polymerase Chain Reaction
  • RNA, Long Noncoding
  • Neurology & Neurosurgery
  • Male
  • Humans
  • Homeostasis
  • Hippocampus
  • Gene Expression Profiling
 

Citation

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Magistri, M., Velmeshev, D., Makhmutova, M., & Faghihi, M. A. (2015). Transcriptomics Profiling of Alzheimer's Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs. J Alzheimers Dis, 48(3), 647–665. https://doi.org/10.3233/JAD-150398
Magistri, Marco, Dmitry Velmeshev, Madina Makhmutova, and Mohammad Ali Faghihi. “Transcriptomics Profiling of Alzheimer's Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs.J Alzheimers Dis 48, no. 3 (2015): 647–65. https://doi.org/10.3233/JAD-150398.
Magistri, Marco, et al. “Transcriptomics Profiling of Alzheimer's Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs.J Alzheimers Dis, vol. 48, no. 3, 2015, pp. 647–65. Pubmed, doi:10.3233/JAD-150398.

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2015

Volume

48

Issue

3

Start / End Page

647 / 665

Location

Netherlands

Related Subject Headings

  • Transcriptome
  • Sequence Analysis, RNA
  • Real-Time Polymerase Chain Reaction
  • RNA, Long Noncoding
  • Neurology & Neurosurgery
  • Male
  • Humans
  • Homeostasis
  • Hippocampus
  • Gene Expression Profiling