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Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.

Publication ,  Journal Article
York, A; Everhart, A; Vitek, MP; Gottschalk, KW; Colton, CA
Published in: ASN Neuro
2021

Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer's disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples. Comparisons were also made between neurons isolated from AD brain sections expressing pathogenic hyperphosphorylated AT8- positive (AT8+) tau and non-AT8+ AD neurons using double labeling techniques. The mRNA expression data showed unique patterns of metabolic pathway expression between the subtypes of captured neurons that involved membrane based solute transporters, redox factors, and arginine and methionine metabolic pathways. We also identified the expression levels of a novel metabolic gene, Radical-S-Adenosyl Domain1 (RSAD1) and its corresponding protein, Rsad1, that impact methionine usage and radical based reactions. Immunohistochemistry was used to identify specific protein expression levels and their cellular location in NeuN+ and AT8+ neurons. APOE4 vs APOE3 genotype-specific and sex-specific gene expression differences in these metabolic pathways were also observed when comparing neurons from individuals with AD to age-matched individuals.

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Published In

ASN Neuro

DOI

EISSN

1759-0914

Publication Date

2021

Volume

13

Start / End Page

17590914211019443

Location

United States

Related Subject Headings

  • tau Proteins
  • Phosphorylation
  • Neurons
  • Male
  • Humans
  • Female
  • Apolipoprotein E4
  • Alzheimer Disease
  • 3209 Neurosciences
  • 1109 Neurosciences
 

Citation

APA
Chicago
ICMJE
MLA
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York, A., Everhart, A., Vitek, M. P., Gottschalk, K. W., & Colton, C. A. (2021). Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease. ASN Neuro, 13, 17590914211019444. https://doi.org/10.1177/17590914211019443
York, Audra, Angela Everhart, Michael P. Vitek, Kirby W. Gottschalk, and Carol A. Colton. “Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.ASN Neuro 13 (2021): 17590914211019444. https://doi.org/10.1177/17590914211019443.
York A, Everhart A, Vitek MP, Gottschalk KW, Colton CA. Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease. ASN Neuro. 2021;13:17590914211019444.
York, Audra, et al. “Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.ASN Neuro, vol. 13, 2021, p. 17590914211019444. Pubmed, doi:10.1177/17590914211019443.
York A, Everhart A, Vitek MP, Gottschalk KW, Colton CA. Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease. ASN Neuro. 2021;13:17590914211019444.
Journal cover image

Published In

ASN Neuro

DOI

EISSN

1759-0914

Publication Date

2021

Volume

13

Start / End Page

17590914211019443

Location

United States

Related Subject Headings

  • tau Proteins
  • Phosphorylation
  • Neurons
  • Male
  • Humans
  • Female
  • Apolipoprotein E4
  • Alzheimer Disease
  • 3209 Neurosciences
  • 1109 Neurosciences