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

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  • Additional Information
    • Source:
      Publisher: International Society of Neuropathology Country of Publication: Switzerland NLM ID: 9216781 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1750-3639 (Electronic) Linking ISSN: 10156305 NLM ISO Abbreviation: Brain Pathol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Zürich, Switzerland : International Society of Neuropathology, [1990-
    • Subject Terms:
      Alzheimer Disease/*metabolism ; Excitatory Amino Acid Transporter 3/*metabolism ; Hippocampus/*metabolism ; Neurons/*metabolism; Aged ; Aged, 80 and over ; Alzheimer Disease/pathology ; Blotting, Western ; Detergents/pharmacology ; Excitatory Amino Acid Transporter 3/chemistry ; Female ; Frontal Lobe/metabolism ; Frontal Lobe/pathology ; Hippocampus/pathology ; Humans ; Immunohistochemistry ; Male ; Neurofibrillary Tangles/metabolism ; Octoxynol/pharmacology ; Parkinson Disease/metabolism ; Parkinson Disease/pathology ; Plaque, Amyloid/metabolism ; Solubility
    • 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.
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    • Grant Information:
      P50 AG005136-25 United States AG NIA NIH HHS; T32 AG000258 United States AG NIA NIH HHS; T32 AG000258-10 United States AG NIA NIH HHS; 5P30 AG 008017 United States AG NIA NIH HHS; P30 AG008017 United States AG NIA NIH HHS; T32 AG 000258 United States AG NIA NIH HHS; P50 AG005136 United States AG NIA NIH HHS; AG 5036 United States AG NIA NIH HHS
    • Accession Number:
      0 (Detergents)
      0 (Excitatory Amino Acid Transporter 3)
      0 (SLC1A1 protein, human)
      9002-93-1 (Octoxynol)
    • Publication Date:
      Date Created: 20080716 Date Completed: 20090501 Latest Revision: 20211020
    • Publication Date:
      20221213
    • Accession Number:
      PMC2657182
    • Accession Number:
      10.1111/j.1750-3639.2008.00186.x
    • Accession Number:
      18624794