Cited by 68Alzheimer's disease research and treatmentsRNA Research and SplicingDementia and Cognitive Impairment Research

Single molecule profiling of tau gene expression in Alzheimer’s disease

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Conrad, Chris, Zhu, Jun, Conrad, Cintia, Schoenfeld, David, Fang, Zhide, Ingelsson, Martin, Stamm, Stefan, Church, George +1 more·2007·Journal of Neurochemistry

Abstract

Tau is a microtubule‐associated protein that is important for establishing and maintaining neuronal morphology. In addition to its role in normal cells, tau protein is involved in many neurodegenerative diseases, e.g. Alzheimer’s disease (AD) and frontotemporal dementia, as the main component of intraneuronal aggregates. Alternative splicing of tau gene in the brain can give rise to at least six protein variants. A causative role of skewed tau exon 10 inclusion has been defined in frontotemporal dementia; however, no link was established between the aberrant splicing of tau and AD. Here, we applied a single‐molecule‐based technology, polymerase colony or polony, to simultaneously monitor tau splicing variant and haplotype profile in sporadic AD and normal brains. We found that the coordinated expression of tau exons 2 and 10 is altered in AD. Additional investigations of cis and trans mechanisms of this observation revealed a decreased protein expression of a known tau splicing factor, htra2‐beta‐1 in AD, thereby implicating a trans mechanism. Our results demonstrate that dysregulation of combinatorial splicing might serve as a signature for aging‐related diseases, and the polony assay could be widely adapted for the study of other tauopathies. Furthermore, splicing‐based therapeutics is an emerging area of drug development, and a well‐defined and quantitative assay for monitoring single‐gene transcriptome will be relevant for such development.

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Crossref · 10.1111/j.1471-4159.2007.04857.x

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  • 4R tau expression is increased in vulnerable brain regions and NFT bearing neurons in AD brain.

    “Expression of tau isoforms in AD brain is complicated; although it is still under debate that whether the overall 3R:4R tau ratio is altered, several studies support a notion that 4R tau expression is increased in vulnerable brain regions and NFT bearing neurons in AD brain [111, 113–118].”

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Research works printed but not linked: 3

  1. Ó 2007 The Authors Journal Compilation Ó 2007 International Society for Neurochemistry, J. Neurochem. (2007) 103, 1228-1236 14714159, 2007, 3, Alzheimer's disease and dementia with Lewy bodies. Neurochem. Res. 28, 1683-1691. · DOI
  2. C. Conrad et al. Journal Compilation Ó 2007 International Society for Neurochemistry, J. Neurochem. (2007) 103, 1228-1236
  3. Ó 2007 The Authors 14714159, 2007, 3, · DOI

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Authors
Conrad, C., Zhu, J., Conrad, C., Schoenfeld, D., Fang, Z., Ingelsson, M., Stamm, S., Church, G., & Hyman, B. T.
Affiliations
  • Massachusetts General Hospital (US)
  • Duke Medical Center (US)
  • LSU New Orleans (US)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Harvard University (US)
Corresponding author
  • Conrad, Chris
  • Zhu, Jun
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2007-07-26
Volume
103
Issue
3
Pages
1228-1236
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2043216798
Cited by
68
References
48
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 3 · 2012: 3
FWCI
3.78
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (P50AG005134)
  • National Human Genome Research Institute
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, alternative splicing, tauopathy
MeSH terms
High-Temperature Requirement A Serine Peptidase 2, Aged, Aged, 80 and over, Alzheimer Disease, Biological Assay, Brain, Brain Chemistry, Exons, Haplotypes, Humans, Molecular Biology, Serine Endopeptidases, Gene Expression, tau Proteins, Alternative Splicing, Genetic Predisposition to Disease, Protein Isoforms, Gene Expression Profiling, Mitochondrial Proteins

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