Detergent-insoluble EAAC1/EAAT3 aberrantly accumulates in hippocampal neurons of Alzheimer's disease patients

Kevin Duerson, Randall L. Woltjer, Paramita Mookherjee, James B. Leverenz, Thomas J. Montine, Thomas D. Bird, David V. Pow, Thomas Rauen, David G. Cook

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Disturbed glutamate homeostasis may contribute to the pathological processes involved in Alzheimer's disease (AD). Once glutamate is released from synapses or from other intracellular sources, it is rapidly cleared by glutamate transporters. EAAC1 (also called EAAT3 or SLC1A1) is the primary glutamate transporter in forebrain neurons. In addition to transporting glutamate, EAAC1 plays other roles in regulating GABA synthesis, reducing oxidative stress in neurons, and is important in supporting neuron viability. Currently, little is known about EAAC1 in AD. To address whether EAAC1 is disturbed in AD, immunohistochemistry was performed on tissue from hippocampus and frontal cortex of AD and normal control subjects matched for age and gender. While EAAC1 immunostaining in cortex appeared comparable to controls, in the hippocampus, EAAC1 aberrantly accumulated in the cell bodies and proximal neuritic processes of CA2-CA3 pyramidal neurons in AD patients. Biochemical analyses showed that Triton X-100-insoluble EAAC1 was significantly increased in the hippocampus of AD patients compared to both controls and Parkinson's disease patients. These findings suggest that aberrant glutamate transporter expression is associated with AD-related neuropathology and that intracellular accumulation of detergent-insoluble EAAC1 is a feature of the complex biochemical lesions in AD that include altered protein solubility.

Original languageEnglish (US)
Pages (from-to)267-278
Number of pages12
JournalBrain Pathology
Volume19
Issue number2
DOIs
StatePublished - Apr 2009

Keywords

  • Excitotoxicity
  • Glutamate Uptake
  • Glutamate toxicity
  • Memantine
  • Neurodegeneration
  • Protein aggregation
  • Synaptic dysfunction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Detergent-insoluble EAAC1/EAAT3 aberrantly accumulates in hippocampal neurons of Alzheimer's disease patients'. Together they form a unique fingerprint.

  • Cite this

    Duerson, K., Woltjer, R. L., Mookherjee, P., Leverenz, J. B., Montine, T. J., Bird, T. D., Pow, D. V., Rauen, T., & Cook, D. G. (2009). Detergent-insoluble EAAC1/EAAT3 aberrantly accumulates in hippocampal neurons of Alzheimer's disease patients. Brain Pathology, 19(2), 267-278. https://doi.org/10.1111/j.1750-3639.2008.00186.x