Hippocampus-specific deficiency in RNA editing of GluA2 in Alzheimer's disease

Inna Gaisler-Salomon, Efrat Kravitz, Yulia Feiler, Michal Safran, Anat Biegon, Ninette Amariglio, Gideon Rechavi

Research output: Contribution to journalArticlepeer-review


Adenosine to inosine (A-to-I) RNA editing is a base recoding process within precursor messenger RNA, catalyzed by members of the adenosine deaminase acting on RNA (ADAR) family. A notable example occurs at the Q/R site of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor subunit GluA2. Abnormally, low editing at this site leads to excessive calcium influx and cell death. We studied hippocampus and caudate samples from Alzheimer's disease (AD) patients and age-matched healthy controls, using direct sequencing and a high accuracy primer-extension technique to assess RNA editing at the Q/R GluA2 site. Both techniques revealed lower, more variable RNA editing in AD, specific to the hippocampus and the GluA2 site. Deficient editing also characterized the hippocampus of apolipoprotein ε4 allele carriers, regardless of clinical diagnosis. In AD, messenger RNA expression of neuronal markers was decreased in the hippocampus, and expression of the Q/R-site editing enzyme ADAR2 was decreased in caudate. These findings provide a link between neurodegenerative processes and deficient RNA editing of the GluA2 Q/R site, and may contribute to both diagnosis and treatment of AD.

Original languageEnglish
Pages (from-to)1785-1791
Number of pages7
JournalNeurobiology of Aging
Issue number8
StatePublished - Aug 2014

Bibliographical note

Funding Information:
This work was supported in part by grants from the Flight Attendant Medical Research Institute , The Molecular Basis of Human Disease I-CORE (Israeli Centers of Research Excellence) and by the Israel Science Foundation (grant numbers 365/06 and 1942/08 ), and the Israel Ministry for Science and Technology (Scientific Infrastructure Program). Gideon Rechavi holds the Djerassi Chair in Oncology at the Sackler Faculty of Medicine, Tel Aviv University. The authors thank Noa Eilat for her help with proofreading the manuscript.


  • ADAR
  • AMPA
  • Alzheimer's disease
  • ApoE
  • Caudate
  • GluA2
  • Glutamate
  • Hippocampus
  • Neurodegeneration
  • Postmortem
  • Primer extension
  • RNA editing

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology


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