Transcriptome Changes in the Alzheimer's Disease Middle Temporal Gyrus: Importance of RNA Metabolism and Mitochondria-Associated Membrane Genes

Ignazio S. Piras, Jonida Krate, Elaine Delvaux, Jennifer Nolz, Diego F. Mastroeni, Antonio M. Persico, Wayne M. Jepsen, Thomas G. Beach, Matthew J. Huentelman, Paul D. Coleman, Colin Combs

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We used Illumina Human HT-12 v4 arrays to compare RNA expression of middle temporal gyrus (MTG; BA21) in Alzheimer's disease (AD=97) and non-demented controls (ND=98). A total of 938 transcripts were highly differentially expressed (adj p<0.01; log2 FC ≥ |0.500|, with 411 overexpressed and 527 underexpressed in AD. Our results correlated with expression profiling in neurons from AD and ND obtained by laser capture microscopy in MTG from an independent dataset (log2 FC correlation: r=0.504; p=2.2e-16). Additionally, selected effects were validated by qPCR. ANOVA analysis yielded no difference between genders in response to AD, but some gender specific genes were detected (e.g., IL8 and AGRN in males, and HSPH1 and GRM1 in females). Several transcripts were associated with Braak staging (e.g., AEBP1 and DNALI1), antemortem MMSE (e.g., AEBP1 and GFAP), and tangle density (e.g., RNU1G2, and DNALI1). At the pathway level, we detected enrichment of synaptic vesicle processes and GABAergic transmission genes. Finally, applying the Weighted Correlation Network Analysis, we identified four expression modules enriched for neuronal and synaptic genes, mitochondria-associated membrane, chemical stimulus and olfactory receptor and non-coding RNA metabolism genes. Our results represent an extensive description of MTG mRNA profiling in a large sample of AD and ND. These data provide a list of genes associated with AD, and correlated to neurofibrillary tangles density. In addition, these data emphasize the importance of mitochondrial membranes and transcripts related to olfactory receptors in AD.

Original languageEnglish (US)
Pages (from-to)691-713
Number of pages23
JournalJournal of Alzheimer's Disease
Volume70
Issue number3
DOIs
StatePublished - Jan 1 2019

Fingerprint

Temporal Lobe
Transcriptome
Alzheimer Disease
Mitochondria
RNA
Membranes
Odorant Receptors
Genes
Untranslated RNA
Neurofibrillary Tangles
Synaptic Vesicles
Mitochondrial Membranes
Interleukin-8
Confocal Microscopy
Analysis of Variance
Neurons
Messenger RNA

Keywords

  • Alzheimer's disease
  • Microarray
  • Middle temporal gyrus
  • Postmortem brains
  • RNA profiling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Transcriptome Changes in the Alzheimer's Disease Middle Temporal Gyrus : Importance of RNA Metabolism and Mitochondria-Associated Membrane Genes. / Piras, Ignazio S.; Krate, Jonida; Delvaux, Elaine; Nolz, Jennifer; Mastroeni, Diego F.; Persico, Antonio M.; Jepsen, Wayne M.; Beach, Thomas G.; Huentelman, Matthew J.; Coleman, Paul D.; Combs, Colin.

In: Journal of Alzheimer's Disease, Vol. 70, No. 3, 01.01.2019, p. 691-713.

Research output: Contribution to journalArticle

Piras, Ignazio S. ; Krate, Jonida ; Delvaux, Elaine ; Nolz, Jennifer ; Mastroeni, Diego F. ; Persico, Antonio M. ; Jepsen, Wayne M. ; Beach, Thomas G. ; Huentelman, Matthew J. ; Coleman, Paul D. ; Combs, Colin. / Transcriptome Changes in the Alzheimer's Disease Middle Temporal Gyrus : Importance of RNA Metabolism and Mitochondria-Associated Membrane Genes. In: Journal of Alzheimer's Disease. 2019 ; Vol. 70, No. 3. pp. 691-713.
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abstract = "We used Illumina Human HT-12 v4 arrays to compare RNA expression of middle temporal gyrus (MTG; BA21) in Alzheimer's disease (AD=97) and non-demented controls (ND=98). A total of 938 transcripts were highly differentially expressed (adj p<0.01; log2 FC ≥ |0.500|, with 411 overexpressed and 527 underexpressed in AD. Our results correlated with expression profiling in neurons from AD and ND obtained by laser capture microscopy in MTG from an independent dataset (log2 FC correlation: r=0.504; p=2.2e-16). Additionally, selected effects were validated by qPCR. ANOVA analysis yielded no difference between genders in response to AD, but some gender specific genes were detected (e.g., IL8 and AGRN in males, and HSPH1 and GRM1 in females). Several transcripts were associated with Braak staging (e.g., AEBP1 and DNALI1), antemortem MMSE (e.g., AEBP1 and GFAP), and tangle density (e.g., RNU1G2, and DNALI1). At the pathway level, we detected enrichment of synaptic vesicle processes and GABAergic transmission genes. Finally, applying the Weighted Correlation Network Analysis, we identified four expression modules enriched for neuronal and synaptic genes, mitochondria-associated membrane, chemical stimulus and olfactory receptor and non-coding RNA metabolism genes. Our results represent an extensive description of MTG mRNA profiling in a large sample of AD and ND. These data provide a list of genes associated with AD, and correlated to neurofibrillary tangles density. In addition, these data emphasize the importance of mitochondrial membranes and transcripts related to olfactory receptors in AD.",
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AU - Nolz, Jennifer

AU - Mastroeni, Diego F.

AU - Persico, Antonio M.

AU - Jepsen, Wayne M.

AU - Beach, Thomas G.

AU - Huentelman, Matthew J.

AU - Coleman, Paul D.

AU - Combs, Colin

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