Changes in hippocampal GABABR1 subunit expression in Alzheimer’s patients: association with Braak staging

Acta Neuropathologica volume 109, pages467–474(2005)Cite this article

Abstract

Alterations in the γ-aminobutyric acid (GABA) neurotransmitter and receptor systems may contribute to vulnerability of hippocampal pyramidal neurons in Alzheimer’s disease (AD). The present study examined the immunohistochemical localization and distribution of GABAB receptor R1 protein (GBR1) in the hippocampus of 16 aged subjects with a range of neurofibrillary tangle (NFT) pathology as defined by Braak staging (I–VI). GBR1 immunoreactivity (IR) was localized to the soma and processes of hippocampal pyramidal cells and some non-pyramidal interneurons. In control subjects (Braak I/II), the intensity of neuronal GBR1 immunostaining differed among hippocampal fields, being most prominent in the CA4 and CA3/2 fields, moderate in the CA1 field, and very light in the dentate gyrus. AD cases with moderate NFT pathology (Braak III/IV) were characterized by increased GBR1-IR, particularly in the CA4 and CA3/2 fields. In the CA1 field of the majority of AD cases, the numbers of GBR1-IR neurons were significantly reduced, despite the presence of Nissl-labeled neurons in this region. These data indicate that GBR1 expression changes with the progression of NFT in AD hippocampus. At the onset of hippocampal pathology, increased or stable expression of GBR1 could contribute to neuronal resistance to the disease process. Advanced hippocampal pathology appears to be associated with decreased neuronal GBR1 staining in the CA1 region, which precedes neuronal cell death. Thus, changes in hippocampal GBR1 may reflect alterations in the balance between excitatory and inhibitory neurotransmitter systems, which likely contributes to dysfunction of hippocampal circuitry in AD.

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Acknowledgements

This work was supported by the NIH grant AG05133, and the Research Grant for Longevity Sciences (14C-4) from the Ministry of Health, Labor and Welfare.

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Affiliations

  1. Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba city, Ibaraki, Japan

    Masahiko Iwakiri, Katsuyoshi Mizukami, Masanori Ishikawa, Shin Hidaka & Takashi Asada

  2. Department of Neurology and Alzheimer’s Disease Research Center, University of Pittsburgh, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA

    Milos D. Ikonomovic, Eric E. Abrahamson & Steven T. DeKosky

Authors
  1. Masahiko Iwakiri
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  2. Katsuyoshi Mizukami
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  3. Milos D. Ikonomovic
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  4. Masanori Ishikawa
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  5. Shin Hidaka
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  6. Eric E. Abrahamson
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Correspondence to Katsuyoshi Mizukami.

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Iwakiri, M., Mizukami, K., Ikonomovic, M.D. et al. Changes in hippocampal GABABR1 subunit expression in Alzheimer’s patients: association with Braak staging. Acta Neuropathol 109, 467–474 (2005). https://doi.org/10.1007/s00401-005-0985-9

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Keywords

  • Alzheimer’s disease
  • GABAB receptor
  • Hippocampus
  • Neuronal degeneration
  • Neurofibrillary tangles